Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients.
Cancer genetics
Cutaneous melanoma
Dermoscopy
Dysplastic nevi
E318K
Germline variant
Melanocyte Inducing Transcription Factor
Nevi
Renal cell carcinoma
Susceptibility
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
13 02 2020
13 02 2020
Historique:
received:
05
05
2019
accepted:
31
01
2020
entrez:
15
2
2020
pubmed:
15
2
2020
medline:
15
5
2021
Statut:
epublish
Résumé
The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF-), including dermoscopic findings of melanomas and dysplastic nevi. we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available. After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF-. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF-). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF- patients, whose most prevalent pattern was the multicomponent. MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF- patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.
Sections du résumé
BACKGROUND
The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF-), including dermoscopic findings of melanomas and dysplastic nevi.
METHODS
we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available.
RESULTS
After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF-. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF-). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF- patients, whose most prevalent pattern was the multicomponent.
CONCLUSIONS
MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF- patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.
Identifiants
pubmed: 32054529
doi: 10.1186/s12967-020-02253-8
pii: 10.1186/s12967-020-02253-8
pmc: PMC7017513
doi:
Substances chimiques
MITF protein, human
0
Microphthalmia-Associated Transcription Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
78Investigateurs
Bruna Dalmasso
(B)
William Bruno
(W)
Lorenza Pastorino
(L)
Virginia Andreotti
(V)
Paola Queirolo
(P)
Francesco Spagnolo
(F)
Enrica Tanda
(E)
Maria Antonietta Pizzichetta
(MA)
Paola Ghiorzo
(P)
Références
Pigment Cell Melanoma Res. 2014 May;27(3):485-8
pubmed: 24406078
J Am Acad Dermatol. 2017 Nov;77(5):938-945.e4
pubmed: 28864306
JAMA Dermatol. 2016 Apr;152(4):405-12
pubmed: 26650189
Int J Cancer. 2007 Aug 15;121(4):825-31
pubmed: 17397031
Nature. 2011 Oct 19;480(7375):94-8
pubmed: 22012259
J Dermatol. 2011 Jan;38(1):16-24
pubmed: 21175751
JAMA Dermatol. 2016 Apr;152(4):375-6
pubmed: 26649449
Melanoma Res. 2018 Apr;28(2):166-169
pubmed: 29485552
Nat Med. 2012 Jan 06;18(1):30-1
pubmed: 22227664
Cancer Manag Res. 2018 May 14;10:1143-1154
pubmed: 29795986
J Am Acad Dermatol. 2016 Feb;74(2):325-32
pubmed: 26775776
Pigment Cell Melanoma Res. 2013 Mar;26(2):259-62
pubmed: 23167872
J Am Acad Dermatol. 2007 Mar;56(3):508-13
pubmed: 17113189
Exp Dermatol. 2012 Sep;21(9):718-20
pubmed: 22804906
Surg Clin North Am. 2020 Feb;100(1):1-12
pubmed: 31753105
Australas J Dermatol. 2012 Nov;53(4):291-4
pubmed: 22497519
Pathobiology. 2016;83(4):165-9
pubmed: 26999813
J Am Acad Dermatol. 2016 Mar;74(3):411-20; quiz 421-2
pubmed: 26892651
J Am Acad Dermatol. 2015 Sep;73(3):507-12
pubmed: 26037217
J Med Genet. 2016 Jan;53(1):1-14
pubmed: 26337759
Ann Transl Med. 2015 Sep;3(15):210
pubmed: 26488006
J Invest Dermatol. 2014 Feb;134(2):481-487
pubmed: 23892592
Am J Dermatopathol. 2014 May;36(5):433-8
pubmed: 24803064
Br J Dermatol. 2017 Aug;177(2):538-540
pubmed: 27681347
Hum Mol Genet. 2006 Sep 15;15(18):2682-9
pubmed: 16893909
Future Oncol. 2013 Feb;9(2):235-44
pubmed: 23414473
Nature. 2011 Nov 13;480(7375):99-103
pubmed: 22080950
J Am Acad Dermatol. 2003 May;48(5):679-93
pubmed: 12734496
Actas Dermosifiliogr. 2014 Sep;105(7):683-93
pubmed: 24704190
J Invest Dermatol. 2014 Jan;134(1):141-149
pubmed: 23774529
J Clin Oncol. 2009 Dec 20;27(36):6199-206
pubmed: 19917835
Ann Surg Oncol. 2018 Aug;25(8):2105-2110
pubmed: 29850954
J Med Genet. 2012 Mar;49(3):164-70
pubmed: 22368299