Prior studies have estimated a small number of individuals with melanoma (2%-2.5%) have germline cancer predisposition, yet a recent twin study suggested melanoma has the highest hereditability among cancers. To determine the incidence of hereditary melanoma and characterize the spectrum of cancer predisposition genes that may increase the risk of melanoma. Four hundred individuals with melanoma and personal or family history of cancers underwent germline testing of >80 cancer predisposition genes. Comparative analysis of germline data was performed on 3 additional oncologic and dermatologic data sets. Germline pathogenic/likely pathogenic (P/LP) variants were identified in 15.3% (61) individuals with melanoma. Most variants (41, 67%) involved genes considered unrelated to melanoma (, ). A third (20, 33%) were in genes previously associated with familial melanoma (). Nearly half (30, 46.9%) of P/LP variants were in homologous repair deficiency genes. Validation cohorts demonstrated P/LP rates of 10.6% from an unselected oncologic cohort, 15.8% from a selected commercial testing cohort, and 14.5% from a highly selected dermatologic study. Cohorts with varying degrees of selection, some retrospective. Germline predisposition in individuals with melanoma is common, with clinically actionable findings diagnosed in 10.6% to 15.8%.

中文翻译：

---

黑色素瘤个体的种系癌易感性

先前的研究估计少数黑色素瘤患者（2%-2.5%）有生殖系癌症倾向，但最近的一项双胞胎研究表明黑色素瘤在癌症中具有最高的遗传性。确定遗传性黑色素瘤的发病率并描述可能增加黑色素瘤风险的癌症易感基因谱。 400 名患有黑色素瘤且有癌症个人或家族史的个体接受了超过 80 个癌症易感基因的种系测试。对另外 3 个肿瘤学和皮肤病学数据集进行了种系数据的比较分析。在 15.3% (61) 的黑色素瘤个体中发现了种系致病性/可能致病性 (P/LP) 变异。大多数变异（41%、67%）涉及被认为与黑色素瘤无关的基因 (, )。第三个 (20, 33%) 存在于先前与家族性黑色素瘤相关的基因中 ()。近一半 (30, 46.9%) 的 P/LP 变异存在于同源修复缺陷基因中。验证队列显示，未选定的肿瘤学队列的 P/LP 率为 10.6%，选定的商业测试队列的 P/LP 率为 15.8%，精心挑选的皮肤病学研究的 P/LP 率为 14.5%。队列有不同程度的选择，有些是回顾性的。黑色素瘤个体的种系易感性很常见，临床上可行的诊断结果为 10.6% 至 15.8%。