Puig Susana, Malvehy Josep, Badenas Cèlia, Ruiz Anna, Jimenez Dolores, Cuellar Francisco, Azon Antoni, Gonzàlez Urbá, Castel Teresa, Campoy Antoni, Herrero Josep, Martí Rosa, Brunet-Vidal Joan, Milà Montserrat
Dermatology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.
J Clin Oncol. 2005 May 1;23(13):3043-51. doi: 10.1200/JCO.2005.08.034.
We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4.
One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included.
Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM.
MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.
我们对一系列连续性多原发性黑色素瘤（MPM）患者进行了研究，以探讨黑色素瘤易感基因座CDKN2A和CDK4的受累情况。
纳入104例MPM患者（81例有两个原发性黑色素瘤，14例有三个，5例有四个，1例有五个，2例有六个，1例有七个）。
在17例患者（16.3%）中鉴定出7种不同的CDKN2A种系突变。我们总共鉴定出15个CDKN2A外显子2、1个外显子1α错义突变和1个外显子1β移码突变。突变患者的发病年龄显著更低，原发性黑色素瘤的数量更多。与无黑色素瘤家族史的患者（8.2%）相比，有黑色素瘤家族史的患者中CDKN2A突变更常见（35.5%），相对风险（RR）为4.32（95%可信区间，1.76至10.64；P = 0.001）；与仅有两个黑色素瘤的患者（10%）相比，有两个以上黑色素瘤的患者中CDKN2A突变更常见（39.1%），RR为3.29（95%可信区间，1.7至6.3；P = 0.002）。MPM患者中A148T多态性比对照人群更常见（P = 0.05）。在1例患者中还检测到1个意义未明的变异体A127S。未鉴定出CDK4突变，提示其对MPM易感性影响较小。
MPM患者是CDKN2A突变筛查的良好对象。这些患者及其部分兄弟姐妹应纳入全身摄影和数字皮肤镜检查的特定随访计划，这将有助于在这一高危患者亚组中早期发现黑色素瘤并改善表型特征。
