Next-generation sequencing revealing TP53 mutation as potential genetic driver in dermal deep-seated melanoma arising in giant congenital nevus in adult patients: A unique case report and review of the literature.
Adult
Biopsy
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Dermis
/ pathology
Female
High-Throughput Nucleotide Sequencing
/ methods
Humans
Immunohistochemistry
/ methods
Lymph Nodes
/ pathology
Male
Melanoma
/ diagnosis
Mutation
Nevus, Pigmented
/ diagnosis
Skin Neoplasms
/ diagnosis
Tumor Suppressor Protein p53
/ genetics
Young Adult
TP53 mutation
giant congenital nevus
melanoma
proliferative nodules
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
10
04
2020
revised:
30
06
2020
accepted:
01
07
2020
pubmed:
10
7
2020
medline:
25
8
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
Melanoma in giant congenital nevus (M-GCN) is a rare and potentially lethal neoplasm. In children, M-GCN appears as a dermal/deep-seated melanoma (DDM-GCN) with histopathologic features difficult to distinguish from proliferative nodules (PNs-GCN). DDM-GCN in adults is an anecdotal entity and only 8 cases have been described and genetically characterized. We report the first case of DDM-GCN in a 34-year-old man characterized with a large-panel next-generation sequence (NGS) highlighting a TP53 mutation with a UV-signature (C>T substitution) in DDM but not in PNs-GCN and GCN. Curiously, DDM showed an aberrant p16 overexpression without detection of CDKN2A mutation at NGS. In line with previous studies, it supports a different pathway in children and adults: UV-induced mutations may be involved in the latter not only by CDKN2A but also by TP53 mutations, with a potentially confusing overexpression of p16 protein. While these data need to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM-GCN.
Substances chimiques
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Case Reports
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1164-1169Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Massi G, Bastian BC, LeBoit PE, Prieto VG, Xu X. Melanoma arising in giant congenital nevus. In: Elder DE, Massi D, Scolyer RA, Willemze R, eds. World Health Organization Classification of Skin Tumours. Lyon, France: IARC Press; 2018:132-133.
Massi G, LeBoit P. Proliferative nodules in congenital and acquired nevi. In: Massi G, LeBoit P, eds. Histological Diagnosis of Nevi and Melanoma. Berlin, Germany: Steinfopgg Verlag Darmstadt; 2014:289-302.
Lambertini M, Baraldi C, Patrizi A, et al. Proliferative melanocytic nodule on small congenital nevus during treatment with etanercept. Am J Dermatopathol. 2018;40(11):871-872.
Pavlova O, Fraitag S, Hohl D. 5-Hydroxymethylcytosine expression in proliferative nodules arising within congenital nevi allows differentiation from malignant melanoma. J Invest Dermatol. 2016;136(12):2453-2461.
Busam KJ, Shah KN, Gerami P, Sitzman T, Jungbluth AA, Kinsler V. Reduced H3K27me3 expression is common in nodular melanomas of childhood associated with congenital melanocytic nevi but not in proliferative nodules. Am J Surg Pathol. 2017;41(3):396-404.
Lu C, Zhang J, Nagahawatte P, et al. The genomic landscape of childhood and adolescent melanoma. J Invest Dermatol. 2015;135(3):816-823.
Phadke PA, Rakheja D, Le LP, et al. Proliferative nodules arising within congenital melanocytic nevi: a histologic, immunohistochemical, and molecular analyses of 43 cases. Am J Surg Pathol. 2011;35(5):656-669.
Fan Y, Lee S, Wu G, et al. Telomerase expression by aberrant methylation of the TERT promoter in melanoma arising in giant congenital nevi. J Invest Dermatol. 2016;136(1):339-342.
Bastian BC, Xiong J, Frieden IJ, et al. Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas. Am J Pathol. 2002;161(4):1163-1169.
Vergier B, Laharanne E, Prochazkova-Carlotti M, et al. Proliferative nodules vs melanoma arising in giant congenital melanocytic nevi during childhood. JAMA Dermatol. 2016;152(10):1147-1151.
Machan S, Molina-Ruiz AM, Fernández-Aceñero MJ, et al. Metastatic melanoma in association with a giant congenital melanocytic nevus in an adult: controversial CGH findings. Am J Dermatopathol. 2015;37(6):487-494.
Wong P, Verselis SJ, Garber JE, et al. Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology. 2006;130(1):73-79.
Masciari S, Dewanwala A, Stoffel EM, et al. Gastric cancer in individuals with Li-Fraumeni syndrome. Genet Med. 2011;13(7):651-657.
Vahteristo P, Tamminen A, Karvinen P, et al. p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Cancer Res. 2001;61(15):5718-5722.
Frebourg T, Barbier N, Yan YX, et al. Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. Am J Hum Genet. 1995;56(3):608-615.
Silwal-Pandit L, Vollan HK, Chin SF, et al. TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance. Clin Cancer Res. 2014;20(13):3569-3580.
Ardighieri L, Mori L, Conzadori S, et al. Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship. Virchows Arch. 2016;469(1):61-69.
Lane DP. Cancer. p53, Guardian of the genome. Nature. 1992;358(6381):15-16.
Carr AM, Green MH, Lehmann AR. Checkpoint policing by p53. Nature. 1992;359(6395):486-487.
Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018;78(2):237-247.
Rayess H, Wang MB, Srivatsan ES. Cellular senescence and tumor suppressor gene p16. Int J Cancer. 2012;130(8):1715-1725.
Rowland BD, Denissov SG, Douma S, Stunnenberg HG, Bernards R, Peeper DS. E2F transcriptional repressor complexes are critical downstream targets of p19(ARF)/p53-induced proliferative arrest. Cancer Cell. 2002;2(1):55-65.
Leong WF, Chau JF, Li B. p53 deficiency leads to compensatory up-regulation of p16INK4a. Mol Cancer Res. 2009;7(3):354-360.
Yamakoshi K, Takahashi A, Hirota F, et al. Real-time in vivo imaging of p16Ink4a reveals cross talk with p53. J Cell Biol. 2009;186(3):393-407.
Siroy AE, Boland GM, Milton DR, et al. Beyond BRAF(V600): clinical mutation panel testing by next-generation sequencing in advanced melanoma. J Invest Dermatol. 2015;135(2):508-515.