Department of Dermatology, University of California, Davis, Sacramento, California, USA.
Hereditary Cancer Program, Comprehensive Cancer Center, University of California, Davis, Sacramento, California, USA.
J Cutan Pathol. 2020 Jul;47(7):606-616. doi: 10.1111/cup.13689. Epub 2020 May 11.
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.
近 15%的黑色素瘤发生在有家族史的患者中，其中一部分患者存在黑色素瘤易感基因的种系突变。CDKN2A 突变是大多数遗传性黑色素瘤的原因，但近年来发现了许多其他易感基因，包括 CDK4、TERT、ACD、TERF2IP、POT1、MITF、MC1R 和 BAP1。此外，由 PTEN、BRCA2、BRCA1、RB1 和 TP53 突变引起的混合癌症综合征会增加黑色素瘤的风险。虽然发病早、多发肿瘤和家族癌症史仍然是遗传性黑色素瘤最有价值的临床线索，但黑色素瘤肿瘤的特征性上皮样细胞学可能提示存在潜在的 BAP1 突变。本文综述了与这些种系突变相关的黑色素瘤肿瘤的临床和组织病理学特征，并讨论了遗传咨询的作用。
