Prevalence of MITF p.E318K in Patients With Melanoma Independent of the Presence of CDKN2A Causative Mutations
Prevalence of MITF p.E318K in Patients With Melanoma Independent of the Presence of CDKN2A Causative Mutations
复制标题
DOI：
10.1001/jamadermatol.2015.4356
复制
发表时间：
2016-04-01
期刊：
影响因子：
10.9
通讯作者：
Puig, Susana
中科院分区：
文献类型：
--
作者：
Potrony, Miriam;Puig-Butille, Joan Anton;Puig, Susana
主要的高外显率黑色素瘤易感基因是CDKN2A，编码p16INK4A和p14ARF。基因MITF变异体p.E318K也易患黑色素瘤和肾细胞癌。迄今为止，尚未在西班牙黑色素瘤患者或p16INK4A突变携带者的单一队列中评估MITF p.E318K的患病率及其临床和表型意义。目的评估MITF p.E318K在西班牙黑色素瘤患者中的患病率，并评估其与临床和表型特征的关系。设计、环境和参与者在巴塞罗那医院诊所黑色素瘤部门进行了一项基于医院的病例对照研究，使用TaqMan探针对所有患者进行MITF p. E318K基因分型。我们纳入了531例患者：271例没有影响p16INK4A（野生型p16INK4A）突变的多发性原发性黑色素瘤（MPM）患者；191个先证者来自黑色素瘤易发家族，诊断单一黑色素瘤且无影响p16INK4A的突变，69个先证者来自不同家族，携带影响p16INK4A的CDKN2A突变。来自西班牙国家DNA银行的499名年龄和性别匹配的无癌症个体作为对照。患者于1992年1月1日至2014年6月30日期间招募；数据分析时间为2014年9月1日至11月30日。MITF p. E318K变异的遗传结果与临床和表型特征相关。结果：在531例患者中，计算了MITF p. E318K变异在所纳入的不同亚群患者中的患病率，在所有p16INK4A野生型黑色素瘤患者中为1.9%（462例中有9例），在MPM患者中为2.6%（271例中有7例），在p16INK4A突变家族的先知者中为2.9%（69例中有2例）。结果报告为优势比（95% CI）， MITF p. E318K与黑色素瘤风险增加相关(3.3 [1.43-7.43]
IMPORTANCE The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previously assessed in a single cohort of Spanish patients with melanoma or in p16INK4A mutation carriers.OBJECTIVES To evaluate the prevalence of MITF p.E318K in Spanish patients with melanoma and assess the association with clinical and phenotypic features.DESIGN, SETTING, AND PARTICIPANTS A hospital-based, case-control study was conducted at the Melanoma Unit of Hospital Clinic of Barcelona, with MITF p. E318K genotyped in all patients using TaqMan probes. We included 531 patients: 271 patients with multiple primary melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families with a single melanoma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carrying CDKN2A mutations affecting p16INK4A. A population-based series of 499 age-and sex-matched cancer-free individuals from the Spanish National Bank of DNA were included as controls. Patients were recruited between January 1, 1992, and June 30, 2014; data analysis was conducted from September 1 to November 30, 2014.MAIN OUTCOMES AND MEASURES The genetic results of the MITF p. E318K variant were correlated with clinical and phenotypic features.RESULTS Among the 531 patients, the prevalence of the MITF p. E318K variant was calculated among the different subsets of patients included and was 1.9%(9 of 462) in all melanoma patients with wild-type p16INK4A, 2.6%(7 of 271) in those with MPM, and 2.9% (2 of 69) in the probands of families with p16INK4A mutations. With results reported as odds ratio (95% CI), the MITF p. E318K was associated with an increased melanoma risk (3.3 [1.43-7.43]; P