Department of Clinical Sciences, Division of Dermatology, Lund Melanoma Study Group, Lund University, Lund, Sweden.
Melanoma Res. 2010 Aug;20(4):266-72. doi: 10.1097/CMR.0b013e3283341339.
Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma. Individuals from eight melanoma-prone families, with index patients carrying the CDKN2A mutation, were offered skin examinations and genotyping (CDKN2A and MC1R). Ninety-three individuals above 18 years of age participated; 29 invasive melanomas in 16 patients were recorded, all in the 38 verified CDKN2A mutation carriers. Median age at diagnosis was 36 years. Several MC1R variants were observed. A significant correlation to CAN (P=0.01) and red hair colour (P=0.02) could be confirmed in melanoma patients. A positive mutation status (CDKN2A) was correlated to one or more CAN (P=0.007) but neither to blue eyes, red hair colour, heavy freckling nor high number of nevi. For mutation carriers, median total naevus count was 24 and interquartile range was 12-47 (mean 31); whereas for the whole cohort, median total naevus count was 12 and interquartile range was 5-25 (mean 22). No participant fulfilled the atypical mole syndrome phenotype criteria. Melanomas were diagnosed only in mutation carriers, and melanoma diagnosis was statistically correlated to the presence of one or more CAN and red hair colour, supporting the possible synergistic effect of a MC1R mutation on increased risk of melanoma in patients with a CDKN2A mutation. Family history, with verified tumour diagnoses, remains an important clinical tool for finding mutation carriers for referral to clinical geneticists and simultaneous presence of CAN in probable mutation carriers might strengthen this indication. The atypical mole syndrome phenotype was, however, not verified in the studied families and total naevus counts were low.
在与 CDKN2A 基因型、痣、临床不典型痣（CAN）和黑色素瘤相关的情况下，检查了易患黑色素瘤的瑞典南部 CDKN2A（p16-113insArg/p14ARF-128insSer）突变家族的表型特征。对 8 个易患黑色素瘤的家族进行了研究，其索引患者携带 CDKN2A 突变，为他们提供了皮肤检查和基因分型（CDKN2A 和 MC1R）。共有 93 名年龄在 18 岁以上的人参加了这项研究；在 16 名患者中发现了 29 例侵袭性黑色素瘤，均发生在 38 名确诊的 CDKN2A 突变携带者中。诊断时的中位年龄为 36 岁。观察到几种 MC1R 变体。在黑色素瘤患者中，可以确认与 CAN（P=0.01）和红发（P=0.02）的显著相关性。阳性突变状态（CDKN2A）与一个或多个 CAN 相关（P=0.007），但与蓝眼睛、红发、重度雀斑或痣的数量无关。对于突变携带者，总痣数的中位数为 24，四分位距为 12-47（平均值为 31）；而对于整个队列，总痣数的中位数为 12，四分位距为 5-25（平均值为 22）。没有参与者符合不典型痣综合征表型标准。黑色素瘤仅在突变携带者中诊断，黑色素瘤的诊断与一个或多个 CAN 和红发的存在呈统计学相关，支持 MC1R 突变与 CDKN2A 突变患者黑色素瘤风险增加的可能协同作用。有经证实的肿瘤诊断的家族史仍然是发现突变携带者并将其转介给临床遗传学家的重要临床工具，而在可能的突变携带者中同时存在 CAN 可能会加强这种指示。然而，在研究的家族中未验证不典型痣综合征表型，且总痣数较低。
