Dermatologia Ente Ospedaliero Cantonale (EOC), Ospedale Regionale Bellinzona e Valli, Bellinzona, Switzerland.
Melanoma Unit, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Br J Dermatol. 2016 Nov;175(5):1030-1037. doi: 10.1111/bjd.14897. Epub 2016 Aug 31.
Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease.
To obtain information about genetic predisposition to CM in Ticino, the southern region of Switzerland, a zone with moderate-to-high CM incidence.
We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. Healthy blood donors (n = 146) were included as a control group.
From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty-six were melanoma-prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83-9·20). At least one MC1R melanoma-associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%).
Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population.
约有 10%的皮肤黑色素瘤（CM）病例发生在有疾病个人或家族史的患者中。
为了获得瑞士南部提契诺地区（CM 发病率中度至高度地区）CM 遗传易感性的相关信息。
我们在多发性原发性 CM 患者或有一个或多个 CM 且一级或二级亲属中有 CM 或胰腺癌阳性家族史的个体中，鉴定了与 CM 高度相关的基因（CDKN2A 和 CDK4）和低/中 penetrance 变体（MC1R 和 MITF）的种系突变。健康献血者（n=146）被纳入对照组。
2010 年 7 月至 2012 年 7 月，共纳入 57 例患者（41 个家系）。26 个为黑色素瘤易感家系（至少有 2 例），15 个为多发性 CM。6 个家系中发现胰腺癌。7 例患者（4 个家系）中发现 CDKN2A p.V126D 突变，呈明显的家族聚集现象，而在 7 例患者（5 个家系）和 7 名健康供者中检测到 CDKN2A A148T（比值比 2.76，95%置信区间 0.83-9.20）。32 例患者（78%）和 97 名健康供者（66%）中至少检测到一个 MC1R 黑色素瘤相关多态性，12 例患者（29%）和 25 名健康供者（17%）中检测到多个多态性。另外 3 个家系中的 4 例患者（7%）和 1 名健康对照者（0.7%）中发现 MITF 变体 p.E318K。
我们的研究结果显示，CDKN2A 突变在近 10%的家系中（41 个家系中的 4 个）、MITF p.E318K 在 7%的家系中（41 个家系中的 3 个）均有发现，且 MC1R 变体的检出率高于对照组。因此，对于提契诺地区的遗传评估，应采用两个受累个体或多发性 CM 患者的纳入标准（两条规则）。
