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Germline mutations predisposing to melanoma
Author(s) -
Toussi Atrin,
Mans Nicole,
Welborn Jeanna,
Kiuru Maija
Publication year - 2020
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.13689
Subject(s) - cdkn2a , bap1 , melanoma , germline mutation , germline , pten , family history , cancer , cowden syndrome , medicine , cancer research , cancer syndrome , mutation , gnaq , pathology , biology , gene , genetics , apoptosis , pi3k/akt/mtor pathway
Nearly 15% of melanomas occur in patients with a family history and a subset of these patients have a germline mutation in a melanoma predisposing gene. CDKN2A mutations are responsible for the majority of hereditary melanoma, but many other susceptibility genes have been discovered in recent years, including CDK4 , TERT , ACD , TERF2IP , POT1 , MITF , MC1R , and BAP1 . Additionally, melanoma risk is increased in mixed cancer syndromes caused by mutations in PTEN , BRCA2 , BRCA1 , RB1 , and TP53 . While early onset, multiple tumors, and family cancer history remain the most valuable clinical clues for hereditary melanoma, characteristic epithelioid cytology of melanocytic tumors may suggest an underlying BAP1 mutation. Herein, we review the clinical and histopathologic characteristics of melanocytic tumors associated with these germline mutations and discuss the role of genetic counseling.