Uveal melanoma.
Journal
Nature reviews. Disease primers
ISSN: 2056-676X
Titre abrégé: Nat Rev Dis Primers
Pays: England
ID NLM: 101672103
Informations de publication
Date de publication:
09 04 2020
09 04 2020
Historique:
accepted:
26
02
2020
entrez:
11
4
2020
pubmed:
11
4
2020
medline:
3
2
2021
Statut:
epublish
Résumé
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year. Risk factors include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma and the BAP1-tumour predisposition syndrome. Ocular treatment aims at preserving the eye and useful vision and, if possible, preventing metastases. Enucleation has largely been superseded by various forms of radiotherapy, phototherapy and local tumour resection, often administered in combination. Ocular outcomes are best with small tumours not extending close to the optic disc and/or fovea. Almost 50% of patients develop metastatic disease, which usually involves the liver, and is usually fatal within 1 year. Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp. Better insight into tumour immunology and metabolism may lead to new treatments.
Identifiants
pubmed: 32273508
doi: 10.1038/s41572-020-0158-0
pii: 10.1038/s41572-020-0158-0
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
24Commentaires et corrections
Type : ErratumIn
Références
Rodrigues, M. et al. So close, yet so far: discrepancies between uveal and other melanomas. A position paper from UM Cure 2020. Cancers 11, e1032 (2019).
Shields, C. L. et al. Iris melanoma: features and prognosis in 317 children and adults. J. Am. Assoc. Pediatr. Ophthalmol. Strabismus 16, 10–16 (2012).
Al-Jamal, R. T. et al. The pediatric choroidal and ciliary body melanoma study. Ophthalmology 123, 898–907 (2016).
Walpole, S. et al. Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide. J. Natl Cancer Inst. 110, 1328–1341 (2018).
pubmed: 6292796
pmcid: 6292796
Royer-Bertrand, B. et al. Comprehensive genetic landscape of uveal melanoma by whole-genome sequencing. Am. J. Hum. Genet. 99, 1190–1198 (2016).
pubmed: 5097942
pmcid: 5097942
de Lange, M. J. et al. Distribution of GNAQ and GNA11 mutation signatures in uveal melanoma points to a light dependent mutation mechanism. PLoS One 10, e0138002 (2015).
pubmed: 4569098
pmcid: 4569098
Furney, S. J. et al. SF3B1 mutations are associated with alternative splicing in uveal melanoma. Cancer Discov. 3, 1122–1129 (2013).
pubmed: 5321577
pmcid: 5321577
Singh, A. D., Rennie, I. G., Seregard, S., Giblin, M. & McKenzie, J. Sunlight exposure and pathogenesis of uveal melanoma. Surv. Ophthalmol. 49, 419–428 (2004).
Sliney, D. H. How light reaches the eye and its components. Int. J. Toxicol. 21, 501–509 (2002).
Li, W., Judge, H., Gragoudas, E. S., Seddon, J. M. & Egan, K. M. Patterns of tumor initiation in choroidal melanoma. Cancer Res. 60, 3757–3760 (2000).
Damato, E. M. & Damato, B. E. Detection and time to treatment of uveal melanoma in the United Kingdom: an evaluation of 2384 patients. Ophthalmology 119, 1582–1589 (2012).
Kujala, E., Mäkitie, T. & Kivelä, T. Very long-term prognosis of patients with malignant uveal melanoma. Invest. Ophthalmol. Vis. Sci. 44, 4651–4659 (2003).
Jensen, O. A. Malignant melanomas of the human uvea: 25-year follow-up of cases in Denmark, 1943–1952. Acta Ophthalmol. 60, 161–182 (1982).
Damato, B. Ocular treatment of choroidal melanoma in relation to the prevention of metastatic death – a personal view. Prog. Retin. Eye Res. 66, 187–199 (2018).
Vader, M. J. C. et al. GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi. Br. J. Cancer 117, 884–887 (2017). This study showed that most regular choroidal naevi carry a mutation in GNAQ or GNA11.
pubmed: 5590000
pmcid: 5590000
Van Raamsdonk, C. D. et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457, 599–602 (2009). This paper first identified the role of GNAQ mutations in the development of UM.
Van Raamsdonk, C. D. et al. Mutations in GNA11 in uveal melanoma. N. Engl. J. Med. 363, 2191–2199 (2010).
pubmed: 3107972
pmcid: 3107972
Robertson, A. G. et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 32, 204–220.e15 (2017). This report describes the use of different platforms to identify four subtypes of UM, each with different genetic, mRNA, long non-coding RNA and epigenetic patterns.
pubmed: 5619925
pmcid: 5619925
Jager, M. J., Brouwer, N. J. & Esmaeli, B. The cancer genome atlas project: an integrated molecular view of uveal melanoma. Ophthalmology 125, 1139–1142 (2018). This paper defines four categories of UM.
Onken, M. D., Worley, L. A., Ehlers, J. P. & Harbour, J. W. Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res. 64, 7205–7209 (2004). Expression of mRNA was used in this study to identify two different patterns, which had prognostic significance and led to the development of a clinical test for the prognostication of UM.
pubmed: 5407684
pmcid: 5407684
Martin, M. et al. Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat. Genet. 45, 933–936 (2013).
pubmed: 4307600
pmcid: 4307600
Maat, W. et al. Monosomy of chromosome 3 and an inflammatory phenotype occur together in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 49, 505–510 (2008).
Harbour, J. W. et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330, 1410–1413 (2010). Mutations in a gene on chromosome 3, BAP1, were discovered in this work and shown to be associated with the development of metastases in UM.
pubmed: 3087380
pmcid: 3087380
Mazloumi, M. et al. Accuracy of the Cancer Genome Atlas classification vs American Joint Committee on Cancer classification for prediction of metastasis in patients with uveal melanoma. JAMA Ophthalmol. 138, 260–267 (2020).
pubmed: 6990957
pmcid: 6990957
Virgili, G. et al. Incidence of uveal melanoma in Europe. Ophthalmology 114, 2309–2315.e2 (2007).
Singh, A. D., Turell, M. E. & Topham, A. K. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 118, 1881–1885 (2011).
Baily, C. et al. Uveal melanoma in Ireland. Ocul. Oncol. Pathol. 5, 195–204 (2019).
Vajdic, C. M. et al. Incidence of ocular melanoma in Australia from 1990 to 1998. Int. J. Cancer 105, 117–122 (2003).
Michalova, K., Clemett, R., Dempster, A., Evans, J. & Allardyce, R. A. Iris melanomas: are they more frequent in New Zealand? Br. J. Ophthalmol. 85, 4–5 (2001).
pubmed: 1723686
pmcid: 1723686
Park, S. J. et al. Nationwide incidence of ocular melanoma in South Korea by using the National Cancer Registry Database (1999–2011). Invest. Ophthalmol. Vis. Sci. 56, 4719–4725 (2015).
Tomizuka, T., Namikawa, K. & Higashi, T. Characteristics of melanoma in Japan: a nationwide registry analysis 2011–2013. Melanoma Res. 27, 492–497 (2017).
Kivela, T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br. J. Ophthalmol. 93, 1129–1131 (2009).
Metzelaar-Blok, J. A. et al. Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients. Invest. Ophthalmol. Vis. Sci. 42, 1951–1954 (2001).
Weis, E., Shah, C. P., Lajous, M., Shields, J. A. & Shields, C. L. The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch. Ophthalmol. 124, 54–60 (2006).
van Hees, C. L. et al. Are atypical nevi a risk factor for uveal melanoma? A case-control study. J. Invest. Dermatol. 103, 202–205 (1994).
van Hees, C. L., Jager, M. J., Bleeker, J. C., Kemme, H. & Bergman, W. Occurrence of cutaneous and uveal melanoma in patients with uveal melanoma and their first degree relatives. Melanoma Res. 8, 175–180 (1998).
Richtig, E., Langmann, G., Müllner, K. & Smolle, J. Ocular melanoma: epidemiology, clinical presentation and relationship with dysplastic nevi. Ophthalmologica 218, 111–114 (2004).
Ferguson, R. et al. Genetic markers of pigmentation are novel risk loci for uveal melanoma. Sci. Rep. 6, 31191 (2016).
pubmed: 4976361
pmcid: 4976361
Schmidt-Pokrzywniak, A., Jöckel, K.-H., Bornfeld, N., Sauerwein, W. & Stang, A. Positive interaction between light iris color and ultraviolet radiation in relation to the risk of uveal melanoma. Ophthalmology 116, 340–348 (2009).
Mobuchon, L. et al. A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus. NPJ Genomic Med. 2, 5 (2017).
James, M. A., Vikis, H. G., Tate, E., Rymaszewski, A. L. & You, M. CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis. Cancer Res. 74, 1116–1127 (2014).
Rodrigues, M. et al. Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors. Nat. Commun. 9, 1866 (2018).
pubmed: 5951831
pmcid: 5951831
Johansson, P. A. et al. Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab. Immunogenetics 71, 433–436 (2019).
Huang, K. et al. Pathogenic germline variants in 10,389 adult cancers. Cell 173, 355–370.e14 (2018).
pubmed: 5949147
pmcid: 5949147
Strande, N. T. et al. Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the clinical genome resource. Am. J. Hum. Genet. 100, 895–906 (2017).
pubmed: 5473734
pmcid: 5473734
Aoude, L. G., Vajdic, C. M., Kricker, A., Armstrong, B. & Hayward, N. K. Prevalence of germline BAP1 mutation in a population-based sample of uveal melanoma cases. Pigment Cell Melanoma Res. 26, 278–279 (2013).
Gupta, M. P. et al. Clinical characteristics of uveal melanoma in patients with germline BAP1 mutations. JAMA Ophthalmol. 133, 881–887 (2015).
Rai, K. et al. Germline BAP1 alterations in familial uveal melanoma: BAP1 in familial uveal melanoma. Genes Chromosomes Cancer 56, 168–174 (2017).
Wiesner, T. et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat. Genet. 43, 1018–1021 (2011).
pubmed: 3328403
pmcid: 3328403
Singh, A. D. et al. Familial uveal melanoma. Clinical observations on 56 patients. Arch. Ophthalmol. 114, 392–399 (1996).
Abdel-Rahman, M. H. et al. Whole exome sequencing identifies candidate genes associated with hereditary predisposition to uveal melanoma. Ophthalmology https://doi.org/10.1016/j.ophtha.2019.11.009 (2019).
doi: 10.1016/j.ophtha.2019.11.009
Lobo, J. et al. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence? Virchows Arch. 470, 347–352 (2017).
Cruz, C., Teule, A., Caminal, J. M., Blanco, I. & Piulats, J. M. Uveal melanoma and BRCA1/BRCA2 genes: a relationship that needs further investigation. J. Clin. Oncol. 29, e827–e829 (2011).
Iscovich, J. et al. Prevalence of the BRCA2 6174 del T mutation in Israeli uveal melanoma patients. Int. J. Cancer 98, 42–44 (2002).
Sinilnikova, O. M. et al. Germline brca2 sequence variants in patients with ocular melanoma. Int. J. Cancer 82, 325–328 (1999).
Marous, C. L., Marous, M. R., Welch, R. J., Shields, J. A. & Shields, C. L. Choroidal melanoma, sector melanocytosis, and retinal pigment epithelial microdetachments in Birt–Hogg–Dubé syndrome. Retin. Cases Brief. Rep. 13, 202–206 (2019).
Fontcuberta, I. C., Salomão, D. R., Quiram, P. A. & Pulido, J. S. Choroidal melanoma and lid fibrofoliculomas in Birt-Hogg-Dubé syndrome. Ophthalmic Genet. 32, 143–146 (2011).
Baglietto, L. et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J. Natl. Cancer Inst. 102, 193–201 (2010).
pubmed: 2815724
pmcid: 2815724
Abdel-Rahman, M. H., Pilarski, R., Ezzat, S., Sexton, J. & Davidorf, F. H. Cancer family history characterization in an unselected cohort of 121 patients with uveal melanoma. Fam. Cancer 9, 431–438 (2010).
Bergman, L., Nilsson, B., Ragnarsson-Olding, B. & Seregard, S. Uveal melanoma: a study on incidence of additional cancers in the Swedish population. Invest. Ophthalmol. Vis. Sci. 47, 72–77 (2006).
Hemminki, K. & Jiang, Y. Association of ocular melanoma with breast cancer but not with cutaneous melanoma: results from the Swedish Family-Cancer Database. Int. J. Cancer 94, 907–909 (2001).
Collaborative Ocular Melanoma Study Group. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch. Ophthalmol. 123, 1639–1643 (2005).
Scélo, G. et al. Associations between ocular melanoma and other primary cancers: an international population-based study. Int. J. Cancer 120, 152–159 (2007).
Nayman, T., Bostan, C., Logan, P. & Burnier, M. N. Uveal melanoma risk factors: a systematic review of meta-analyses. Curr. Eye Res. 42, 1085–1093 (2017).
Holly, E. A., Aston, D. A., Ahn, D. K. & Smith, A. H. Intraocular melanoma linked to occupations and chemical exposures. Epidemiol. Camb. Mass. 7, 55–61 (1996).
Napolitano, A. et al. Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene 35, 1996–2002 (2016).
Betti, M. et al. Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes. Genes Chromosomes Cancer 57, 573–583 (2018).
Stang, A. et al. Mobile phone use and risk of uveal melanoma: results of the risk factors for uveal melanoma case-control study. J. Natl. Cancer Inst. 101, 120–123 (2009).
pubmed: 2639317
pmcid: 2639317
Beahm, A. No evidence of Auburn ocular melanoma cluster, Alabama health department says. AL.com https://www.al.com/news/2018/10/adph-no-evidence-of-rare-eye-cancer-cluster-in-auburn.html (2018).
North Carolina Department of Health and Human Services Division of Public Health. Ocular Melanoma Investigation in Mecklenburg County, North Carolina. https://epi.dph.ncdhhs.gov/oee/docs/OcularMelanomaInvestigationReport_June2015.pdf (2015).
Wakamatsu, K., Hu, D.-N., McCormick, S. A. & Ito, S. Characterization of melanin in human iridal and choroidal melanocytes from eyes with various colored irides. Pigment Cell Melanoma Res. 21, 97–105 (2008).
Ni-Komatsu, L. & Orlow, S. J. Heterologous expression of tyrosinase recapitulates the misprocessing and mistrafficking in oculocutaneous albinism type 2: effects of altering intracellular pH and pink-eyed dilution gene expression. Exp. Eye Res. 82, 519–528 (2006).
Toyofuku, K. et al. The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase. Pigment Cell Res. 15, 217–224 (2002).
Fuller, B. B., Iman, D. S. & Lunsford, J. B. Comparison of tyrosinase levels in amelanotic and melanotic melanoma cell cultures by a competitive enzyme-linked immunoadsorbent assay and by immunotitration analysis. J. Cell. Physiol. 134, 149–154 (1988).
Lee, Y. et al. Characteristics of melanosomes in melanotic and amelanotic melanomas. J. Hard Tissue Biol. 13, 87–90 (2004).
Field, M. G. et al. Punctuated evolution of canonical genomic aberrations in uveal melanoma. Nat. Commun. 9, 116 (2018).
pubmed: 5760704
pmcid: 5760704
Moore, A. R. et al. Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat. Genet. 48, 675–680 (2016).
pubmed: 5032652
pmcid: 5032652
Johansson, P. et al. Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4. Oncotarget 7, 4624–4631 (2016).
Yoo, J. H. et al. ARF6 is an actionable node that orchestrates oncogenic GNAQ signaling in uveal melanoma. Cancer Cell 29, 889–904 (2016).
pubmed: 5027844
pmcid: 5027844
Yu, F.-X. et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25, 822–830 (2014).
pubmed: 4075337
pmcid: 4075337
Feng, X. et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 25, 831–845 (2014).
pubmed: 4074519
pmcid: 4074519
Feng, X. et al. A platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the hippo pathway through FAK. Cancer Cell 35, 457–472.e5 (2019).
pubmed: 6737937
pmcid: 6737937
Yasui, F., Miyazu, M., Yoshida, A., Naruse, K. & Takai, A. Examination of signalling pathways involved in muscarinic responses in bovine ciliary muscle using YM-254890, an inhibitor of the Gq/11 protein. Br. J. Pharmacol. 154, 890–900 (2008).
pubmed: 2439854
pmcid: 2439854
Lapadula, D. et al. Effects of oncogenic Gαq and Gα11 inhibition by FR900359 in uveal melanoma. Mol. Cancer Res. 17, 963–973 (2019).
Singh, A. D., Kalyani, P. & Topham, A. Estimating the risk of malignant transformation of a choroidal nevus. Ophthalmology 112, 1784–1789 (2005).
Carbone, M. et al. BAP1 and cancer. Nat. Rev. Cancer 13, 153–159 (2013).
pubmed: 3792854
pmcid: 3792854
Bononi, A. et al. BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature 546, 549–553 (2017).
pubmed: 5581194
pmcid: 5581194
Field, M. G. et al. BAP1 loss is associated with DNA methylomic repatterning in highly aggressive class 2 uveal melanomas. Clin. Cancer Res. 25, 5663–5673 (2019).
pubmed: 6744995
pmcid: 6744995
Scheuermann, J. C. et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465, 243–247 (2010).
pubmed: 3182123
pmcid: 3182123
Wang, L. et al. Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy. Nat. Med. 24, 758–769 (2018).
pubmed: 6055231
pmcid: 6055231
Campagne, A. et al. BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation. Nat. Commun. 10, 348 (2019).
pubmed: 6341105
pmcid: 6341105
Harbour, J. W. et al. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat. Genet. 45, 133–135 (2013).
pubmed: 3789378
pmcid: 3789378
Darman, R. B. et al. Cancer-associated SF3B1 hotspot mutations induce cryptic 3′ splice site selection through use of a different branch point. Cell Rep. 13, 1033–1045 (2015).
Alsafadi, S. et al. Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. Nat. Commun. 7, 10615 (2016).
pubmed: 4743009
pmcid: 4743009
Inoue, D. et al. Spliceosomal disruption of the non-canonical BAF complex in cancer. Nature 574, 432–436 (2019).
pubmed: 6858563
pmcid: 6858563
Johnson, C. P. et al. Systematic genomic and translational efficiency studies of uveal melanoma. PLoS One 12, e0178189 (2017).
pubmed: 5464544
pmcid: 5464544
Shields, C. L. et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch. Ophthalmol. 127, 989–998 (2009). An analysis of a very large group of UMs showing that tumour size plays an important part in the development of metastases.
Zimmerman, L. E., McLean, I. W. & Foster, W. D. Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells. Br. J. Ophthalmol. 62, 420–425 (1978).
pubmed: 1043246
pmcid: 1043246
Singh, A. D. The Zimmerman-Mclean-Foster hypothesis: 25 years later. Br. J. Ophthalmol. 88, 962–967 (2004).
pubmed: 1772246
pmcid: 1772246
Yavuzyigitoglu, S. et al. Uveal melanomas with SF3B1 mutations: a distinct subclass associated with late-onset metastases. Ophthalmology 123, 1118–1128 (2016).
Szalai, E. et al. Association of uveal melanoma metastatic rate with stochastic mutation rate and type of mutation. JAMA Ophthalmol. 136, 1115–1120 (2018).
pubmed: 6233840
pmcid: 6233840
Koopmans, A. E. et al. Clinical significance of immunohistochemistry for detection of BAP1 mutations in uveal melanoma. Mod. Pathol. 27, 1321–1330 (2014). This study demonstrated that immunohistochemistry can be used for determining prognosis based on expression of BAP1.
van Essen, T. H. et al. Prognostic parameters in uveal melanoma and their association with BAP1 expression. Br. J. Ophthalmol. 98, 1738–1743 (2014).
Szalai, E., Wells, J. R., Ward, L. & Grossniklaus, H. E. Uveal melanoma nuclear BRCA1-associated protein-1 immunoreactivity is an indicator of metastasis. Ophthalmology 125, 203–209 (2018).
Shain, A. H. et al. The genetic evolution of metastatic uveal melanoma. Nat. Genet. 51, 1123–1130 (2019).
pubmed: 6632071
pmcid: 6632071
Rodrigues, M. et al. Evolutionary routes in metastatic uveal melanomas depend on MBD4 alterations. Clin. Cancer Res. 25, 5513–5524 (2019).
Piaggio, F. et al. Secondary somatic mutations in G-protein-related pathways and mutation signatures in uveal melanoma. Cancers 11, E1688 (2019).
Eide, N. et al. Disseminated tumour cells in bone marrow of patients with uveal melanoma. Acta Ophthalmol. 91, 343–348 (2013).
Eide, N. et al. Immunomagnetic detection of micrometastatic cells in bone marrow in uveal melanoma patients. Acta Ophthalmol. 87, 830–836 (2009).
Sadegh, L., Chen, P. W., Brown, J. R., Han, Z. & Niederkorn, J. Y. NKT cells act through third party bone marrow-derived cells to suppress NK cell activity in the liver and exacerbate hepatic melanoma metastases: NKT cells and ocular melanoma liver metastases. Int. J. Cancer 137, 1085–1094 (2015).
pubmed: 4537411
pmcid: 4537411
Hendrix, M. J. et al. Regulation of uveal melanoma interconverted phenotype by hepatocyte growth factor/scatter factor (HGF/SF). Am. J. Pathol. 152, 855–863 (1998).
pubmed: 1858259
pmcid: 1858259
Yu, G. et al. Hepatic stellate cells secreted hepatocyte growth factor contributes to the chemoresistance of hepatocellular carcinoma. PLoS One 8, e73312 (2013).
pubmed: 3759390
pmcid: 3759390
Diaz, C. E., Rusciano, D., Dithmar, S. & Grossniklaus, H. E. B16LS9 melanoma cells spread to the liver from the murine ocular posterior compartment (PC). Curr. Eye Res. 18, 125–129 (1999).
Li, H., Yang, W., Chen, P. W., Alizadeh, H. & Niederkorn, J. Y. Inhibition of chemokine receptor expression on uveal melanomas by CXCR4 siRNA and its effect on uveal melanoma liver metastases. Invest. Ophthalmol. Vis. Sci. 50, 5522–5528 (2009).
Li, H., Alizadeh, H. & Niederkorn, J. Y. Differential expression of chemokine receptors on uveal melanoma cells and their metastases. Invest. Ophthalmol. Vis. Sci. 49, 636–643 (2008).
Liepelt, A. & Tacke, F. Stromal cell-derived factor-1 (SDF-1) as a target in liver diseases. Am. J. Physiol. Gastrointest. Liver Physiol. 311, G203–G209 (2016).
Zhu, A. et al. Dipyrimidine amines: a novel class of chemokine receptor type 4 antagonists with high specificity. J. Med. Chem. 53, 8556–8568 (2010).
pubmed: 3003753
pmcid: 3003753
Dong, L. et al. Arylsulfonamide 64B inhibits hypoxia/HIF-induced expression of c-Met and CXCR4 and reduces primary tumor growth and metastasis of uveal melanoma. Clin. Cancer Res. 25, 2206–2218 (2019).
Grossniklaus, H. E. et al. Metastatic ocular melanoma to the liver exhibits infiltrative and nodular growth patterns. Hum. Pathol. 57, 165–175 (2016).
pubmed: 5547398
pmcid: 5547398
Jones, N. M., Yang, H., Zhang, Q., Morales-Tirado, V. M. & Grossniklaus, H. E. Natural killer cells and pigment epithelial-derived factor control the infiltrative and nodular growth of hepatic metastases in an orthotopic murine model of ocular melanoma. BMC Cancer 19, 484 (2019).
pubmed: 6532210
pmcid: 6532210
Liao, A. et al. Radiologic and histopathologic correlation of different growth patterns of metastatic uveal melanoma to the liver. Ophthalmology 125, 597–605 (2018).
Grossniklaus, H. E. Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman Lecture. JAMA Ophthalmol. 131, 462–469 (2013). This paper highlights that not all metastases are the same, which may have implications for the treatment of liver metastases.
pubmed: 4472306
pmcid: 4472306
Eefsen, R. L. et al. Histopathological growth pattern, proteolysis and angiogenesis in chemonaive patients resected for multiple colorectal liver metastases. J. Oncol. 2012, 1–12 (2012).
Nwani, N. G. et al. Melanoma cells block PEDF production in fibroblasts to induce the tumor-promoting phenotype of cancer-associated fibroblasts. Cancer Res. 76, 2265–2276 (2016).
pubmed: 4873437
pmcid: 4873437
Niederkorn, J., Streilein, J. W. & Shadduck, J. A. Deviant immune responses to allogeneic tumors injected intracamerally and subcutaneously in mice. Invest. Ophthalmol. Vis. Sci. 20, 355–363 (1981). The phenomenon of anterior chamber-associated immune deviation is described in this paper.
Schurmans, L. R. et al. Successful immunotherapy of an intraocular tumor in mice. Cancer Res. 59, 5250–5254 (1999).
Streilein, J. W. & Niederkorn, J. Y. Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J. Exp. Med. 153, 1058–1067 (1981).
Niederkorn, J. Y. Immune escape mechanisms of intraocular tumors. Prog. Retin. Eye Res. 28, 329–347 (2009).
pubmed: 2727063
pmcid: 2727063
Jiang, L. Q., Jorquera, M. & Streilein, J. W. Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Invest. Ophthalmol. Vis. Sci. 34, 3347–3354 (1993).
Knisely, T. L., Luckenbach, M. W., Fischer, B. J. & Niederkorn, J. Y. Destructive and nondestructive patterns of immune rejection of syngeneic intraocular tumors. J. Immunol. 138, 4515–4523 (1987).
Thorsson, V. et al. The immune landscape of cancer. Immunity 48, 812–830.e14 (2018).
pubmed: 5982584
pmcid: 5982584
de Waard-Siebinga, I., Hilders, C. G. J. M., Hansen, B. E., van Delft, J. L. & Jager, M. J. HLA expression and tumor-infiltrating immune cells in uveal melanoma. Graefes Arch. Clin. Exp. Ophthalmol. 234, 34–42 (1996).
Davidorf, F. H. & Lang, J. R. Lymphocytic infiltration in choroidal melanoma and its prognostic significance. Trans. Ophthalmol. Soc. UK 97, 394–401 (1977).
Tobal, K., Deuble, K., McCartney, A. & Lightman, S. Characterization of cellular infiltration in choroidal melanoma. Melanoma Res. 3, 63–65 (1993).
Bronkhorst, I. H. G. et al. Different subsets of tumor-infiltrating lymphocytes correlate with macrophage influx and monosomy 3 in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 53, 5370–5378 (2012).
Lagouros, E. et al. Infiltrative T regulatory cells in enucleated uveal melanomas. Trans. Am. Ophthalmol. Soc. 107, 223–228 (2009).
pubmed: 2814577
pmcid: 2814577
Gezgin, G. et al. Genetic evolution of uveal melanoma guides the development of an inflammatory microenvironment. Cancer Immunol. Immunother. 66, 903–912 (2017).
pubmed: 5489616
pmcid: 5489616
Figueiredo, C. R. et al. Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development. J. Pathol. 250, 420–439 (2020).
pubmed: 7216965
pmcid: 7216965
McGranahan, N. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351, 1463–1469 (2016).
pubmed: 4984254
pmcid: 4984254
Colli, L. M. et al. Burden of nonsynonymous mutations among TCGA cancers and candidate immune checkpoint inhibitor responses. Cancer Res. 76, 3767–3772 (2016).
pubmed: 4930685
pmcid: 4930685
van der Pol, J. P. et al. Heterogeneous expression of melanoma-associated antigens in uveal melanomas. Curr. Eye Res. 6, 757–765 (1987).
de Vries, T. J., Trancikova, D., Ruiter, D. J. & van Muijen, G. N. High expression of immunotherapy candidate proteins gp100, MART-1, tyrosinase and TRP-1 in uveal melanoma. Br. J. Cancer 78, 1156–1161 (1998).
pubmed: 2063001
pmcid: 2063001
Mulcahy, K. A. et al. Infrequent expression of the MAGE gene family in uveal melanomas. Int. J. Cancer 66, 738–742 (1996).
Field, M. G. et al. PRAME as an independent biomarker for metastasis in uveal melanoma. Clin. Cancer Res. 22, 1234–1242 (2016).
pubmed: 4780366
pmcid: 4780366
Gezgin, G. et al. PRAME as a potential target for immunotherapy in metastatic uveal melanoma. JAMA Ophthalmol. 135, 541–549 (2017).
pubmed: 5509351
pmcid: 5509351
Garrido, F. & Algarra, I. MHC antigens and tumor escape from immune surveillance. Adv. Cancer Res. 83, 117–158 (2001).
Anastassiou, G., Rebmann, V., Wagner, S., Bornfeld, N. & Grosse-Wilde, H. Expression of classic and nonclassic HLA class I antigens in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 44, 2016–2019 (2003).
Blom, D. J. et al. Human leukocyte antigen class I expression. Marker of poor prognosis in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 38, 1865–1872 (1997).
Ericsson, C. et al. Association of HLA class I and class II antigen expression and mortality in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 42, 2153–2156 (2001).
Dithmar, S., Crowder, J., Jager, M. J., Vigniswaran, N. & Grossniklaus, H. E. HLA class I antigen expression correlates with histological cell type in uveal melanoma. Ophthalmology 99, 625–628 (2002).
Jager, M. J., Hurks, H. M., Levitskaya, J. & Kiessling, R. HLA expression in uveal melanoma: there is no rule without some exception. Hum. Immunol. 63, 444–451 (2002).
Dithmar, S., Rusciano, D., Armstrong, C. A., Lynn, M. J. & Grossniklaus, H. E. Depletion of NK cell activity results in growth of hepatic micrometastases in a murine ocular melanoma model. Curr. Eye Res. 19, 426–431 (1999).
Ma, D., Luyten, G. P., Luider, T. M. & Niederkorn, J. Y. Relationship between natural killer cell susceptibility and metastasis of human uveal melanoma cells in a murine model. Invest. Ophthalmol. Vis. Sci. 36, 435–441 (1995).
Souri, Z., Wierenga, A. P. A., Mulder, A., Jochemsen, A. G. & Jager, M. J. HLA expression in uveal melanoma: an indicator of malignancy and a modifiable immunological target. Cancers 11, 1132 (2019).
pubmed: 6721545
pmcid: 6721545
van Essen, T. H. et al. Upregulation of HLA expression in primary uveal melanoma by infiltrating leukocytes. PLoS One 11, e0164292 (2016).
pubmed: 5072555
pmcid: 5072555
de Waard-Siebinga, I., Creyghton, W. M., Kool, J. & Jager, M. J. Effects of interferon alfa and gamma on human uveal melanoma cells in vitro. Br. J. Ophthalmol. 79, 847–855 (1995).
pubmed: 505272
pmcid: 505272
Mäkitie, T., Summanen, P., Tarkkanen, A. & Kivelä, T. Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma. Invest. Ophthalmol. Vis. Sci. 40, 2471–2480 (1999).
Mäkitie, T., Summanen, P., Tarkkanen, A. & Kivelä, T. Tumor-infiltrating macrophages (CD68+ cells) and prognosis in malignant uveal melanoma. Invest. Ophthalmol. Vis. Sci. 42, 1414–1421 (2001). This study found that the presence of tumour-infiltrating macrophages is associated with poor prognosis.
Bronkhorst, I. H. G. et al. Detection of M2-macrophages in uveal melanoma and relation with survival. Invest. Ophthalmol. Vis. Sci. 52, 643–650 (2011). This study demonstrated that in UM, infiltrating macrophages are proangiogenic, explaining their association with poor prognosis; proangiogenic macrophages help the formation of blood vessels, which are essential for metastasis.
Brouwer, N. J. et al. Tumour angiogenesis in uveal melanoma is related to genetic evolution. Cancers 11, E979 (2019).
McKenna, K. C. et al. Activated CD11b+ CD15+ granulocytes increase in the blood of patients with uveal melanoma. Invest. Ophthalmol. Vis. Sci. 50, 4295–4303 (2009).
Carlring, J., Shaif-Muthana, M., Sisley, K., Rennie, I. G. & Murray, A. K. Apoptotic cell death in conjunction with CD80 costimulation confers uveal melanoma cells with the ability to induce immune responses. Immunology 109, 41–48 (2003).
pubmed: 1782946
pmcid: 1782946
Bosch, J. J. et al. MHC class II-transduced tumor cells originating in the immune-privileged eye prime and boost CD4(+) T lymphocytes that cross-react with primary and metastatic uveal melanoma cells. Cancer Res. 67, 4499–4506 (2007).
Verbik, D. J., Murray, T. G., Tran, J. M. & Ksander, B. R. Melanomas that develop within the eye inhibit lymphocyte proliferation. Int. J. Cancer 73, 470–478 (1997).
Wierenga, A. P. A., Cao, J., Luyten, G. P. M. & Jager, M. J. Immune checkpoint inhibitors in uveal and conjunctival melanoma. Int. Ophthalmol. Clin. 59, 53–63 (2019).
Durante, M. A. et al. Single-cell analysis reveals new evolutionary complexity in uveal melanoma. Nat. Commun. 11, 496 (2020).
pubmed: 6981133
pmcid: 6981133
Yang, W. et al. PD-L1 expression on human ocular cells and its possible role in regulating immune-mediated ocular inflammation. Invest. Ophthalmol. Vis. Sci. 50, 273–280 (2009).
Hallermalm, K. et al. Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes. J. Immunol. 180, 3766–3774 (2008).
Chen, P. W. et al. Uveal melanoma expression of indoleamine 2,3-deoxygenase: establishment of an immune privileged environment by tryptophan depletion. Exp. Eye Res. 85, 617–625 (2007).
pubmed: 2695208
pmcid: 2695208
Felberg, N. T., Donoso, L. A. & Federman, J. L. Tumor-associated antibodies in the serum of patients with ocular melanoma. IV. Correction for smooth muscle antibodies. Ophthalmol. 87, 529–533 (1980).
Rahi, A. H. Autoimmune reactions in uveal melanoma. Br. J. Ophthalmol. 55, 793–807 (1971).
pubmed: 1208589
pmcid: 1208589
Goslings, W. R. et al. Membrane-bound regulators of complement activation in uveal melanomas. CD46, CD55, and CD59 in uveal melanomas. Invest. Ophthalmol. Vis. Sci. 37, 1884–1891 (1996).
Kan-Mitchell, J. et al. Lymphocytes cytotoxic to uveal and skin melanoma cells from peripheral blood of ocular melanoma patients. Cancer Immunol. Immunother. 33, 333–340 (1991).
Ksander, B. R. et al. Uveal melanomas contain antigenically specific and non-specific infiltrating lymphocytes. Curr. Eye Res. 17, 165–173 (1998).
Ksander, B. R., Rubsamen, P. E., Olsen, K. R., Cousins, S. W. & Streilein, J. W. Studies of tumor-infiltrating lymphocytes from a human choroidal melanoma. Invest. Ophthalmol. Vis. Sci. 32, 3198–3208 (1991).
Rothermel, L. D. et al. Identification of an immunogenic subset of metastatic uveal melanoma. Clin. Cancer Res. 22, 2237–2249 (2016).
Chandran, S. S. et al. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol. 18, 792–802 (2017).
pubmed: 5490083
pmcid: 5490083
Krishna, Y., McCarthy, C., Kalirai, H. & Coupland, S. E. Inflammatory cell infiltrates in advanced metastatic uveal melanoma. Hum. Pathol. 66, 159–166 (2017).
Foster, A. D., Sivarapatna, A. & Gress, R. E. The aging immune system and its relationship with cancer. Aging Health 7, 707–718 (2011).
pubmed: 3222953
pmcid: 3222953
Sandinha, T., Hebbar, G., Kenawy, N., Hope-Stone, L. & Damato, B. A nurse-led ocular oncology clinic in Liverpool: results of a 6-month trial. Eye 26, 937–943 (2012).
pubmed: 3396164
pmcid: 3396164
Smith, J. R. et al. Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference. Transl. Vis. Sci. Technol. 8, 9 (2019).
pubmed: 6333107
pmcid: 6333107
Shields, J. A. & Shields, C. L. Management of posterior uveal melanoma: past, present, and future: the 2014 Charles L. Schepens Lecture. Ophthalmology 122, 414–428 (2015).
Kivelä, T. Diagnosis of uveal melanoma. Dev. Ophthalmol. 49, 1–15 (2012).
Dogrusöz, M., Jager, M. J. & Damato, B. Uveal melanoma treatment and prognostication. Asia-Pac. J. Ophthalmol. 6, 186–196 (2017).
Shields, C. L., Manalac, J., Das, C., Ferguson, K. & Shields, J. A. Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas. Curr. Opin. Ophthalmol. 25, 177–185 (2014).
Shields, C. L. et al. Clinical survey of 3680 iris tumors based on patient age at presentation. Ophthalmology 119, 407–414 (2012).
Shields, C. L., Kaliki, S., Furuta, M., Mashayekhi, A. & Shields, J. A. Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina 32, 1363–1372 (2012).
Shields, C. L. et al. Visual outcome and millimeter incremental risk of metastasis in 1780 patients with small choroidal melanoma managed by plaque radiotherapy. JAMA Ophthalmol. 136, 1325–1333 (2018).
pubmed: 6583692
pmcid: 6583692
Shields, C. L. et al. Large uveal melanoma (≥10 mm thickness): clinical features and millimeter-by-millimeter risk of metastasis in 1311 cases. The 2018 Albert E. Finley Lecture. Retina 38, 2010–2022 (2018).
Shields, C. L. et al. Choroidal nevus imaging features in 3,806 cases and risk factors for transformation into melanoma in 2,355 cases: the 2020 Taylor R. Smith and Victor T. Curtin Lecture. Retina 39, 1840–1851 (2018). This paper defines the characteristics of naevi that transform into UM.
Coleman, D. J. et al. High-resolution ultrasonic imaging of the posterior segment. Ophthalmology 111, 1344–1351 (2004).
Lois, N. Cavitary melanoma of the ciliary body A study of eight cases. Ophthalmology 105, 1091–1098 (1998).
Nordlund, J. R., Robertson, D. M. & Herman, D. C. Ultrasound biomicroscopy in management of malignant iris melanoma. Arch. Ophthalmol. 121, 725–727 (2003).
Bianciotto, C. et al. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ophthalmology 118, 1297–1302 (2011).
Damato, B. E. Tumour fluorescence and tumour-associated fluorescence of choroidal melanomas. Eye 6, 587–593 (1992).
Damato, B. E. & Foulds, W. S. Tumour-associated retinal pigment epitheliopathy. Eye 4, 382–387 (1990).
Shields, C. L., Shields, J. A. & De Potter, P. Patterns of indocyanine green videoangiography of choroidal tumours. Br. J. Ophthalmol. 79, 237–245 (1995).
pubmed: 505071
pmcid: 505071
Shields, C. L. et al. Autofluorescence of choroidal melanoma in 51 cases. Br. J. Ophthalmol. 92, 617–622 (2008).
Shields, C. L. et al. Autofluorescence of choroidal nevus in 64 cases. Retina 28, 1035–1043 (2008).
Shields, C. L., Bianciotto, C., Pirondini, C. & Shields, J. A. Autofluorescence of intraocular tumors. Invest. Ophthalmol. Vis. Sci. 49, 5689–5689 (2008).
Bindewald-Wittich, A., Swenshon, T., Carasco, E., Dreyhaupt, J. & Willerding, G. D. Blue-light fundus autofluorescence imaging following ruthenium-106 brachytherapy for choroidal melanoma. Ophthalmologica https://doi.org/10.1159/000504715 (2020).
doi: 10.1159/000504715
Muscat, S. Secondary retinal changes associated with choroidal naevi and melanomas documented by optical coherence tomography. Br. J. Ophthalmol. 88, 120–124 (2004).
pubmed: 1771938
pmcid: 1771938
Singh, A. D., Belfort, R. N., Sayanagi, K. & Kaiser, P. K. Fourier domain optical coherence tomographic and auto-fluorescence findings in indeterminate choroidal melanocytic lesions. Br. J. Ophthalmol. 94, 474–478 (2010).
Shah, S. U. et al. Enhanced depth imaging optical coherence tomography of choroidal nevus in 104 cases. Ophthalmol. 119, 1066–1072 (2012).
Shields, C. L., Pellegrini, M., Ferenczy, S. R. & Shields, J. A. Enhanced depth imaging optical coherence tomography of intraocular tumors: from placid to seasick to rock and rolling topography — the 2013 Francesco Orzalesi Lecture. Retina 34, 1495–1512 (2014).
Damato, B. E., Heimann, H., Kalirai, H. & Coupland, S. E. Age, survival predictors, and metastatic death in patients with choroidal melanoma: tentative evidence of a therapeutic effect on survival. JAMA Ophthalmol. 132, 605–613 (2014).
Shields, C., Manalac, J., Saktanasate, J., Shields, J. & Das, C. Review of spectral domain enhanced depth imaging optical coherence tomography of tumors of the choroid. Indian. J. Ophthalmol. 63, 117–121 (2015).
pubmed: 4399119
pmcid: 4399119
Valverde-Megías, A., Say, E. A. T., Ferenczy, S. R. & Shields, C. L. Differential macular features on optical coherence tomography angiography in eyes with choroidal nevus and melanoma. Retina 37, 731–740 (2017).
Shields, C. L. et al. Optical coherence tomography angiography of the macula after plaque radiotherapy of choroidal melanoma: comparison of irradiated versus nonirradiated eyes in 65 patients. Retina 36, 1493–1505 (2016).
Brouwer, N. J. et al. Retinal oximetry is altered in eyes with choroidal melanoma but not in eyes with choroidal nevi. Retina https://doi.org/10.1097/IAE.0000000000002719 (2019).
doi: 10.1097/IAE.0000000000002719
pubmed: 7575014
pmcid: 7575014
Beenakker, J.-W. M. et al. Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning. MAGMA 29, 571–577 (2016).
pubmed: 4891368
pmcid: 4891368
Tartaglione, T. et al. Uveal melanoma: evaluation of extrascleral extension using thin-section MR of the eye with surface coils. Radiol. Med. 119, 775–783 (2014).
Ferreira, T. et al. MRI of uveal melanoma. Cancers 11, E377 (2019).
Shields, J. A., Shields, C. L., Ehya, H., Eagle, R. C. & De Potter, P. Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology 100, 1677–1684 (1993).
Midena, E. et al. In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy. Eur. J. Ophthalmol. 16, 422–425 (2006).
Shields, C. L. et al. Personalized prognosis of uveal melanoma based on cytogenetic profile in 1059 patients over an 8-year period. Ophthalmology 124, 1523–1531 (2017).
Shields, C. L. et al. Prognosis of uveal melanoma in 500 cases using genetic testing of fine-needle aspiration biopsy specimens. Ophthalmology 118, 396–401 (2011).
Shields, C. L. et al. Cytogenetic abnormalities in uveal melanoma based on tumor features and size in 1059 patients. Ophthalmology 124, 609–618 (2017).
Scholes, A. G. M. et al. Monosomy 3 in uveal melanoma: correlation with clinical and histologic predictors of survival. Invest. Ophthalmol. Vis. Sci. 44, 1008–1011 (2003).
Callender, G. R. Malignant melanotic tumors of the eye: a study of histologic types in 111 cases. Trans. Am. Acad. Ophthalmol. Otolaryngol. 36, 131–140 (1931).
McLean, I. W., Foster, W. D., Zimmerman, L. E. & Gamel, J. W. Modifications of Callender’s classification of uveal melanoma at the Armed Forces Institute of Pathology. Am. J. Ophthalmol. 96, 502–509 (1983).
Fernandes, B. F. et al. Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma. J. Carcinog. 6, 6 (2007).
pubmed: 1864985
pmcid: 1864985
O’Reilly, F. M. et al. Microphthalmia transcription factor immunohistochemistry: a useful diagnostic marker in the diagnosis and detection of cutaneous melanoma, sentinel lymph node metastases, and extracutaneous melanocytic neoplasms. J. Am. Acad. Dermatol. 45, 414–419 (2001).
Mouriaux, F. et al. Expression of the c-kit receptor in choroidal melanomas. Melanoma Res. 13, 161–166 (2003).
Amin, M. B. et al. The eighth edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more ‘personalized’ approach to cancer staging. CA. Cancer J. Clin. 67, 93–99 (2017).
Folberg, R. et al. The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology 100, 1389–1398 (1993).
Shields, J. A. & Shields, C. L. Intraocular Tumors: An Atlas and Textbook 3rd edn (Wolters Kluwer, 2015).
Damato, B. Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye 26, 1157–1172 (2012).
pubmed: 3443832
pmcid: 3443832
Manschot, W. A. & Van Strik, R. Is irradiation a justifiable treatment of choroidal melanoma? Analysis of published results. Br. J. Ophthalmol. 71, 348–352 (1987).
pubmed: 1041164
pmcid: 1041164
Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch. Ophthalmol. 119, 969–982 (2001).
Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch. Ophthalmol. 124, 1684–1693 (2006).
Collaborative Ocular Melanoma Study Group. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report number 24. Am. J. Ophthalmol. 138, 936–951 (2004).
Sagoo, M. S. et al. Plaque radiotherapy for juxtapapillary choroidal melanoma: tumor control in 650 consecutive cases. Ophthalmology 118, 402–407 (2011).
Shields, C. L. et al. Iris melanoma management with iodine-125 plaque radiotherapy in 144 patients: impact of melanoma-related glaucoma on outcomes. Ophthalmology 120, 55–61 (2013).
Gündüz, K., Shields, C. L., Shields, J. A., Cater, J. & Brady, L. Plaque radiotherapy for management of ciliary body and choroidal melanoma with extraocular extension. Am. J. Ophthalmol. 130, 97–102 (2000).
Shah, S. U. et al. Intravitreal bevacizumab at 4-month intervals for prevention of macular edema after plaque radiotherapy of uveal melanoma. Ophthalmology 121, 269–275 (2014).
Gragoudas, E. S., Lane, A. M., Munzenrider, J., Egan, K. M. & Li, W. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans. Am. Ophthalmol. Soc. 100, 43–48 (2002).
pubmed: 1358945
pmcid: 1358945
Damato, B. in Retinal Vascular Disease (eds Joussen, A. M., Gardner, T. W., Kirchhof, B. & Ryan, S. J.) 582–591 (Springer, 2007).
Shields, C. L., Shields, J. A., Gündüz, K., Freire, J. E. & Mercado, G. Radiation therapy for uveal malignant melanoma. Ophthalmic Surg. Lasers 29, 397–409 (1998).
Lommatzsch, P. & Vollmar, R. A new way in the conservative therapy of intraocular tumors by means of beta-irradiation (ruthenium 106) with preservation of vision [German]. Klin. Monatsbl. Augenheilkd. 148, 682–699 (1966).
Horgan, N. et al. Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: a randomized controlled trial. Ophthalmology 116, 1383–1390 (2009).
Shields, C. L. et al. Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients. Arch. Ophthalmol. 118, 1219–1228 (2000).
Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology 108, 348–366 (2001).
Gragoudas, E. S. et al. Proton beam irradiation. An alternative to enucleation for intraocular melanomas. Ophthalmology 87, 571–581 (1980).
Gragoudas, E. S. Proton beam irradiation of uveal melanomas: the first 30 years. The Weisenfeld Lecture. Invest. Ophthalmol. Vis. Sci. 47, 4666–4673 (2006).
Damato, B. et al. Proton beam radiotherapy of iris melanoma. Int. J. Radiat. Oncol. Biol. Phys. 63, 109–115 (2005).
Akbaba, S. et al. Linear accelerator-based stereotactic fractionated photon radiotherapy as an eye-conserving treatment for uveal melanoma. Radiat. Oncol. 13, 140 (2018).
pubmed: 6090919
pmcid: 6090919
Siedlecki, J. et al. Incidence of secondary glaucoma after treatment of uveal melanoma with robotic radiosurgery versus brachytherapy. Acta Ophthalmol. 95, e734–e739 (2017).
Oosterhuis, J. A., Journée-de Korver, H. G. & Keunen, J. E. Transpupillary thermotherapy: results in 50 patients with choroidal melanoma. Arch. Ophthalmol. 116, 157–162 (1998).
Shields, C. L., Shields, J. A., Perez, N., Singh, A. D. & Cater, J. Primary transpupillary thermotherapy for small choroidal melanoma in 256 consecutive cases: outcomes and limitations. Ophthalmology 109, 225–234 (2002).
Mashayekhi, A. et al. Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: importance of risk factors in tumor control. Ophthalmology 122, 600–609 (2015).
Marinkovic, M. et al. Ruthenium-106 brachytherapy for choroidal melanoma without transpupillary thermotherapy: similar efficacy with improved visual outcome. Eur. J. Cancer 68, 106–113 (2016).
Blasi, M. A. et al. Brachytherapy alone or with neoadjuvant photodynamic therapy for amelanotic choroidal melanoma: functional outcomes and local tumor control. Retina 36, 2205–2212 (2016).
Campbell, W. G. & Pejnovic, T. M. Treatment of amelanotic choroidal melanoma with photodynamic therapy. Retina 32, 1356–1362 (2012).
Turkoglu, E. B., Pointdujour-Lim, R., Mashayekhi, A. & Shields, C. L. Photodynamic therapy as primary treatment for small choroidal melanoma. Retina 39, 1319–1325 (2018).
Rundle, P. Treatment of posterior uveal melanoma with multi-dose photodynamic therapy. Br. J. Ophthalmol. 98, 494–497 (2014).
Shields, C. L., Lim, L.-A. S., Dalvin, L. A. & Shields, J. A. Small choroidal melanoma: detection with multimodal imaging and management with plaque radiotherapy or AU-011 nanoparticle therapy. Curr. Opin. Ophthalmol. 30, 206–214 (2019).
Kines, R. C. et al. An infrared dye-conjugated virus-like particle for the treatment of primary uveal melanoma. Mol. Cancer Ther. 17, 565–574 (2018).
Damato, B. E., Afshar, R., Stewart, J., Groenwald, C. & Foulds, W. S. in Retina Vol. 3 (ed. Ryan, S. J.) 2298–2306 (Elsevier, 2013).
Shields, J. A., Shields, C. L., Shah, P. & Sivalingam, V. Partial lamellar sclerouvectomy for ciliary body and choroidal tumors. Ophthalmology 98, 971–983 (1991).
Damato, B. The role of eyewall resection in uveal melanoma management. Int. Ophthalmol. Clin. 46, 81–93 (2006).
Kivelä, T., Puusaari, I. & Damato, B. Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness. Ophthalmology 110, 2235–2244 (2003).
Bechrakis, N. E. & Foerster, M. H. Neoadjuvant proton beam radiotherapy combined with subsequent endoresection of choroidal melanomas. Int. Ophthalmol. Clin. 46, 95–107 (2006).
Konstantinidis, L., Groenewald, C., Coupland, S. E. & Damato, B. Long-term outcome of primary endoresection of choroidal melanoma. Br. J. Ophthalmol. 98, 82–85 (2014).
Barker, C. A. & Salama, A. K. New NCCN guidelines for uveal melanoma and treatment of recurrent or progressive distant metastatic melanoma. J. Natl Compr. Cancer Netw. 16, 646–650 (2018).
Bellerive, C. et al. Local failure after episcleral brachytherapy for posterior uveal melanoma: patterns, risk factors, and management. Am. J. Ophthalmol. 177, 9–16 (2017).
AJCC Ophthalmic Oncology Task Force. International validation of the American Joint Committee on Cancer’s 7th Edition Classification of Uveal Melanoma. JAMA Ophthalmol. 133, 376–383 (2015).
Gündüz, K. et al. Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement. Am. J. Ophthalmol. 127, 579–589 (1999).
Wisely, C. E. et al. Long-term visual acuity outcomes in patients with uveal melanoma treated with 125I episcleral OSU-Nag plaque brachytherapy. Brachytherapy 15, 12–22 (2016).
pubmed: 4990815
pmcid: 4990815
Horgan, N. et al. Periocular triamcinolone for prevention of macular edema after iodine 125 plaque radiotherapy of uveal melanoma. Retina 28, 987–995 (2008).
Materin, M. A., Bianciotto, C. G., Wu, C. & Shields, C. L. Sector laser photocoagulation for the prevention of macular edema after plaque radiotherapy for uveal melanoma: a pilot study. Retina 32, 1601–1607 (2012).
DeParis, S. W. et al. External validation of the Liverpool uveal melanoma prognosticator online. Invest. Ophthalmol. Vis. Sci. 57, 6116–6122 (2016).
Valsecchi, M. E. et al. Adjuvant sunitinib in high-risk patients with uveal melanoma: comparison with institutional controls. Ophthalmology 125, 210–217 (2018).
McLean, M. J., Foster, W. D. & Zimmerman, L. E. Prognostic factors in small malignant melanomas of choroid and ciliary body. Arch. Ophthalmol. 95, 48–58 (1977).
de la Cruz, P. O., Specht, C. S. & McLean, I. W. Lymphocytic infiltration in uveal malignant melanoma. Cancer 65, 112–115 (1990).
Prescher, G., Bornfeld, N., Horsthemke, B. & Becher, R. Chromosomal aberrations defining uveal melanoma of poor prognosis. Lancet 339, 691–692 (1992).
Horsman, D. E., Sroka, H., Rootman, J. & White, V. A. Monosomy 3 and isochromosome 8q in a uveal melanoma. Cancer Genet. Cytogenet. 45, 249–253 (1990). This paper provides the first description of the presence of specific chromosomal aberrations in primary UM.
Sisley, K. et al. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes. Chromosomes Cancer 19, 22–28 (1997).
White, V. A., Chambers, J. D., Courtright, P. D., Chang, W. Y. & Horsman, D. E. Correlation of cytogenetic abnormalities with the outcome of patients with uveal melanoma. Cancer 83, 354–359 (1998).
Damato, B. et al. Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology 114, 1925–1931 (2007).
Damato, B., Eleuteri, A., Taktak, A. F. G. & Coupland, S. E. Estimating prognosis for survival after treatment of choroidal melanoma. Prog. Retin. Eye Res. 30, 285–295 (2011).
Cassoux, N. et al. Genome-wide profiling is a clinically relevant and affordable prognostic test in posterior uveal melanoma. Br. J. Ophthalmol. 98, 769–774 (2014).
Tschentscher, F. et al. Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res. 63, 2578–2584 (2003).
Dogrusöz, M. & Jager, M. J. Genetic prognostication in uveal melanoma. Acta Ophthalmol. 96, 331–347 (2018).
Dogrusöz, M. et al. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest. Ophthalmol. Vis. Sci. 58, 833 (2017).
Bagger, M. et al. The prognostic effect of American Joint Committee on Cancer staging and genetic status in patients with choroidal and ciliary body melanoma. Invest. Ophthalmol. Vis. Sci. 56, 438–444 (2014).
Onken, M. D. et al. Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology 119, 1596–1603 (2012).
Eleuteri, A., Damato, B., Coupland, S. E. & Taktak, A. F. G. Enhancing survival prognostication in patients with choroidal melanoma by integrating pathologic, clinical and genetic predictors of metastasis. Int. J. Biomed. Eng. Technol. 8, 18–35 (2012).
Vaquero-Garcia, J. et al. PRiMeUM: a model for predicting risk of metastasis in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 58, 4096–4105 (2017).
pubmed: 6108308
pmcid: 6108308
Nathan, P. et al. Uveal melanoma UK national guidelines. Eur. J. Cancer 51, 2404–2412 (2015).
Ritsma, L. et al. Intravital microscopy through an abdominal imaging window reveals a pre-micrometastasis stage during liver metastasis. Sci. Transl. Med. 4, 158ra145 (2012).
Richtig, E. et al. Safety and efficacy of interferon alfa-2b in the adjuvant treatment of uveal melanoma [German]. Ophthalmologe 103, 506–511 (2006).
Lane, A. M. et al. Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis. Ophthalmology 116, 2206–2212 (2009).
McLean, I. W. et al. A randomized study of methanol-extraction residue of bacille Calmette-Guerin as postsurgical adjuvant therapy of uveal melanoma. Am. J. Ophthalmol. 110, 522–526 (1990).
Desjardins, L. et al. Etude randomisée de chimiothérapie adjuvante par le Déticène dans le mélanome choroïdien [French]. Ophtalmologie 12, 168–173 (1998).
Desjardins, L. et al. Adjuvant intravenous therapy by fotemustine in uveal melanoma: a randomised study [abstract]. Acta Ophthalmol. https://doi.org/10.1111/j.1755-3768.2011.4362.x (2011).
doi: 10.1111/j.1755-3768.2011.4362.x
Leyvraz, S. et al. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann. Oncol. 25, 742–746 (2014).
pubmed: 4433517
pmcid: 4433517
Hughes, M. S. et al. Results of a randomized controlled multicenter phase III trial of percutaneous hepatic perfusion compared with best available care for patients with melanoma liver metastases. Ann. Surg. Oncol. 23, 1309–1319 (2016).
Bhatia, S. et al. Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. PLoS One 7, e48787 (2012).
pubmed: 3511501
pmcid: 3511501
Homsi, J. et al. Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in patients with metastatic uveal melanoma. Melanoma Res. 20, 507–510 (2010).
O’Neill, P. A., Butt, M., Eswar, C. V., Gillis, P. & Marshall, E. A prospective single arm phase II study of dacarbazine and treosulfan as first-line therapy in metastatic uveal melanoma. Melanoma Res. 16, 245–248 (2006).
Schmittel, A. et al. Phase II trial of cisplatin, gemcitabine and treosulfan in patients with metastatic uveal melanoma. Melanoma Res. 15, 205–207 (2005).
Schmittel, A. et al. A two-cohort phase II clinical trial of gemcitabine plus treosulfan in patients with metastatic uveal melanoma. Melanoma Res. 15, 447–451 (2005).
Schmidt-Hieber, M., Schmittel, A., Thiel, E. & Keilholz, U. A phase II study of bendamustine chemotherapy as second-line treatment in metastatic uveal melanoma. Melanoma Res. 14, 439–442 (2004).
Bedikian, A. Y., Papadopoulos, N., Plager, C., Eton, O. & Ring, S. Phase II evaluation of temozolomide in metastatic choroidal melanoma. Melanoma Res. 13, 303–306 (2003).
Kivelä, T. et al. Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur. J. Cancer 39, 1115–1120 (2003).
Carvajal, R. D. et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA 311, 2397–2405 (2014).
pubmed: 24938562
pmcid: 24938562
Carvajal, R. D. et al. Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (SUMIT). J. Clin. Oncol. 36, 1232–1239 (2018).
Piperno-Neumann, S. et al. Phase I dose-escalation study of the protein kinase C (PKC) inhibitor AEB071 in patients with metastatic uveal melanoma [abstract]. J. Clin. Oncol. 32 (Suppl. 15), 9030 (2014).
Kapiteijn, E. et al. A phase I trial of LXS196, a novel PKC inhibitor for metastatic uveal melanoma [abstract]. Cancer Res. 79 (Suppl. 13), CT068 (2019).
Onken, M. D. et al. Targeting nucleotide exchange to inhibit constitutively active G protein α subunits in cancer cells. Sci. Signal. 11, eaao6852 (2018).
pubmed: 6279241
pmcid: 6279241
Ambrosini, G., Sawle, A. D., Musi, E. & Schwartz, G. K. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells. Oncotarget 6, 33397–33409 (2015).
pubmed: 4741774
pmcid: 4741774
Chua, V. et al. Stromal fibroblast growth factor 2 reduces the efficacy of bromodomain inhibitors in uveal melanoma. EMBO Mol. Med. 11, e9081 (2019).
pubmed: 6365926
pmcid: 6365926
Zimmer, L. et al. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma. PloS One 10, e0118564 (2015).
pubmed: 4356548
pmcid: 4356548
Joshua, A. M. et al. A phase 2 study of tremelimumab in patients with advanced uveal melanoma. Melanoma Res. 25, 342–347 (2015).
Algazi, A. P. et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer 122, 3344–3353 (2016).
Piulats, J. M. et al. Phase II multicenter, single arm, open label study of nivolumab (NIVO) in combination with ipilimumab (IPI) as first line in adult patients (pts) with metastatic uveal melanoma (MUM): GEM1402 NCT02626962 [abstract]. J. Clin. Oncol. 35 (Suppl. 15), 9533 (2017).
Damato, B. E., Dukes, J., Goodall, H. & Carvajal, R. D. Tebentafusp: T cell redirection for the treatment of metastatic uveal melanoma. Cancers 11, E971 (2019).
Meijer, T. S. et al. Safety of percutaneous hepatic perfusion with melphalan in patients with unresectable liver metastases from ocular melanoma using the delcath systems’ second-generation hemofiltration system: a prospective non-randomized phase II trial. Cardiovasc. Intervent. Radiol. 42, 841–852 (2019).
pubmed: 6502784
pmcid: 6502784
Damato, B. et al. Patient-reported outcomes and quality of life after treatment of choroidal melanoma: a comparison of enucleation versus radiotherapy in 1596 patients. Am. J. Ophthalmol. 193, 230–251 (2018). This study evaluated the outcomes of different approaches to treat UM from the perspective of the patient.
Damato, B. et al. Patient-reported outcomes and quality of life after treatment for choroidal melanoma. Ocul. Oncol. Pathol. 5, 402–411 (2019).
pubmed: 6873060
pmcid: 6873060
Afshar, A. R., Deiner, M., Allen, G. & Damato, B. E. The patient’s experience of ocular melanoma in the US: a survey of the Ocular Melanoma Foundation. Ocul. Oncol. Pathol. 4, 280–290 (2018).
pubmed: 6170915
pmcid: 6170915
Dogrusöz, M. et al. Differential expression of DNA repair genes in prognostically-favorable versus unfavorable uveal melanoma. Cancers 11, E1104 (2019).
Doherty, R. E., Bryant, H. E., Valluru, M. K., Rennie, I. G. & Sisley, K. Increased non-homologous end joining makes DNA-PK a promising target for therapeutic intervention in uveal melanoma. Cancers 11, E1278 (2019).
Zhang, B., Wu, H., Hao, J., Wu, Y. & Yang, B. Inhibition of DNA-PKcs activity re-sensitizes uveal melanoma cells to radio- and chemotherapy. Biochem. Biophys. Res. Commun. 522, 639–646 (2020).
Ophthalmic Oncology Task Force. Local recurrence significantly increases the risk of metastatic uveal melanoma. Ophthalmology 123, 86–91 (2016).
Davidorf, F. H. The melanoma controversy. A comparison of choroidal, cutaneous, and iris melanomas. Surv. Ophthalmol. 25, 373–377 (1981).
Apt, L. Uveal melanomas in children and adolescents. Int. Ophthalmol. Clin. 2, 403–410 (1962).
Shields, C. L. et al. Uveal melanoma in teenagers and children. A report of 40 cases. Ophthalmology 98, 1662–1666 (1991).
Scholz, S. L. et al. Frequent GNAQ, GNA11, and EIF1AX mutations in iris melanoma. Invest. Ophthalmol. Vis. Sci. 58, 3464–3470 (2017).
Krishna, Y. et al. Genetic findings in treatment-naïve and proton-beam-radiated iris melanomas. Br. J. Ophthalmol. 100, 1012–1016 (2016).
van Poppelen, N. M. et al. Genetic background of iris melanomas and iris melanocytic tumors of uncertain malignant potential. Ophthalmology 125, 904–912 (2018).
Harbour, J. W., Wilson, D., Finger, P. T., Worley, L. A. & Onken, M. D. Gene expressing profiling of iris melanomas. Ophthalmology 120, 213–213.e3 (2013).
Shields, C. L. et al. Iris nevus growth into melanoma: analysis of 1611 consecutive eyes. Ophthalmology 120, 766–772 (2013).
Shields, C. L. et al. Iris melanoma outcomes based on the American Joint Committee on Cancer classification (eighth edition) in 432 patients. Ophthalmology 125, 913–923 (2018).
Popovic, M., Ahmed, I. I. K., DiGiovanni, J. & Shields, C. L. Radiotherapeutic and surgical management of iris melanoma: a review. Surv. Ophthalmol. 62, 302–311 (2017).
Thariat, J. et al. Proton beam therapy for iris melanomas in 107 patients. Ophthalmology 125, 606–614 (2018).
Gokhale, R., Medina, C. A., Biscotti, C. V. & Singh, A. D. Diagnostic fine-needle aspiration biopsy for iris melanoma. Asia-Pac. J. Ophthalmol. 4, 89–91 (2015).
Petousis, V., Finger, P. T. & Milman, T. Anterior segment tumor biopsy using an aspiration cutter technique: clinical experience. Am. J. Ophthalmol. 152, 771–775.e1 (2011).
Camp, D. A., Yadav, P., Dalvin, L. A. & Shields, C. L. Glaucoma secondary to intraocular tumors: mechanisms and management. Curr. Opin. Ophthalmol. 30, 71–81 (2019).
Kaliki, S. & Shields, C. L. Focal Points 2015 Module: Choroidal Nevus. American Academy of Ophthalmology (2015).
Qiu, M. & Shields, C. L. Choroidal nevus in the United States adult population: racial disparities and associated factors in the National Health and Nutrition Examination Survey. Ophthalmology 122, 2071–2083 (2015).
Kelland, L. R. “Of mice and men”: values and liabilities of the athymic nude mouse model in anticancer drug development. Eur. J. Cancer 40, 827–836 (2004).
Cao, J. & Jager, M. J. Animal eye models for uveal melanoma. Ocul. Oncol. Pathol. 1, 141–150 (2015).
pubmed: 4847684
pmcid: 4847684
Braun, R. D. & Vistisen, K. S. Modeling human choroidal melanoma xenograft growth in immunocompromised rodents to assess treatment efficacy. Invest. Ophthalmol. Vis. Sci. 53, 2693 (2012).
pubmed: 3357116
pmcid: 3357116
Gao, M., Tang, J., Liu, K., Yang, M. & Liu, H. Quantitative evaluation of vascular microcirculation using contrast-enhanced ultrasound imaging in rabbit models of choroidal melanoma. Invest. Ophthalmol. Vis. Sci. 59, 1251 (2018).
Ent, Wvander et al. Modeling of human uveal melanoma in zebrafish xenograft embryos. Invest. Ophthalmol. Vis. Sci. 55, 6612–6622 (2014).
Amirouchene-Angelozzi, N. et al. Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target. Mol. Oncol. 8, 1508–1520 (2014).
pubmed: 5528590
pmcid: 5528590
Jager, M., Magner, J., Ksander, B. & Dubovy, S. Uveal melanoma cell lines: where do they come from? (an American Ophthalmological Society Thesis). Trans. Am. Ophthalmol. Soc. 114, T5 (2016).
pubmed: 5161001
pmcid: 5161001
Siolas, D. & Hannon, G. J. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 73, 5315–5319 (2013).
pubmed: 3766500
pmcid: 3766500
Hidalgo, M. et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 4, 998–1013 (2014).
pubmed: 4167608
pmcid: 4167608
Huang, J. L.-Y., Urtatiz, O. & Van Raamsdonk, C. D. Oncogenic G protein GNAQ induces uveal melanoma and intravasation in mice. Cancer Res. 75, 3384–3397 (2015).
Perez, D. E., Henle, A. M., Amsterdam, A., Hagen, H. R. & Lees, J. A. Uveal melanoma driver mutations in GNAQ/11 yield numerous changes in melanocyte biology. Pigment Cell Melanoma Res. 31, 604–613 (2018).
pubmed: 6151293
pmcid: 6151293
Moore, A. R. et al. GNA11 Q209L mouse model reveals RasGRP3 as an essential signaling node in uveal melanoma. Cell Rep. 22, 2455–2468 (2018).
pubmed: 5854482
pmcid: 5854482
Ozaki, S. et al. Establishment and characterization of orthotopic mouse models for human uveal melanoma hepatic colonization. Am. J. Pathol. 186, 43–56 (2016).
pubmed: 4715216
pmcid: 4715216
Folberg, R. et al. Modeling the behavior of uveal melanoma in the liver. Invest. Ophthalmol. Vis. Sci. 48, 2967–2974 (2007).
Papakostas, T. D., Lane, A. M., Morrison, M., Gragoudas, E. S. & Kim, I. K. Long-term outcomes after proton beam irradiation in patients with large choroidal melanomas. JAMA Ophthalmol. 135, 1191–1196 (2017).
pubmed: 5710395
pmcid: 5710395
Furdova, A. et al. Clinical experience of stereotactic radiosurgery at a linear accelerator for intraocular melanoma. Melanoma Res. 27, 463–468 (2017).
Wackernagel, W. et al. Local tumour control and eye preservation after gamma-knife radiosurgery of choroidal melanomas. Br. J. Ophthalmol. 98, 218–223 (2014).
Blasi, M. A. et al. Photodynamic therapy in ocular oncology. Biomedicines 6, 17 (2018).
pubmed: 5874674
pmcid: 5874674
Fabian, I. D. et al. Primary photodynamic therapy with verteporfin for pigmented posterior pole cT1a choroidal melanoma: a 3-year retrospective analysis. Br. J. Ophthalmol. 102, 1705–1710 (2018).
Cassoux, N. et al. Choroidal melanoma: does endoresection prevent neovascular glaucoma in patient treated with proton beam irradiation? Retina 33, 1441–1447 (2013).
Brovkina, A. F. Local treatment of choroidal melanoma: possibilities and limitations. Vestn. Oftalmol. 134, 52–60 (2018).
Rice, J. C. et al. Brachytherapy and endoresection for choroidal melanoma: a cohort study. Br. J. Ophthalmol. 98, 86–91 (2014).
Vidoris, A. A. C. et al. Outcomes of primary endoresection for choroidal melanoma. Int. J. Retina Vitr. 3, 42 (2017).
Hirobe, T., Ito, S. & Wakamatsu, K. The mouse pink-eyed dilution allele of the P-gene greatly inhibits eumelanin but not pheomelanin synthesis: the pink-eyed dilution gene and melanin. Pigment. Cell Melanoma Res. 24, 241–246 (2011).
Pellosi, M. C. et al. Effects of the melanin precursor 5,6-dihydroxy-indole-2-carboxylic acid (DHICA) on DNA damage and repair in the presence of reactive oxygen species. Arch. Biochem. Biophys. 557, 55–64 (2014).
Rogers, M. S. et al. The classical pink-eyed dilution mutation affects angiogenic responsiveness. PLoS One 7, e35237 (2012).
pubmed: 3352893
pmcid: 3352893
Wakamatsu, K., Hirobe, T. & Ito, S. High levels of melanin-related metabolites in plasma from pink-eyed dilution mice. Pigment Cell Res. 20, 222–224 (2007).
Vivet-Noguer, R., Tarin, M., Roman-Roman, S. & Alsafadi, S. Emerging therapeutic opportunities based on current knowledge of uveal melanoma biology. Cancers 11, E1019 (2019).
Grossniklaus, H. E. Understanding uveal melanoma metastasis to the liver: the Zimmerman effect and the Zimmerman hypothesis. Ophthalmology 126, 483–487 (2019).