Galore Gilli, Azizi Esther, Scope Alon, Pavlotsky Felix, Yakobson Emanuel, Friedman Eitan
Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.
Melanoma Res. 2007 Apr;17(2):105-8. doi: 10.1097/CMR.0b013e3280c31d81.
MC1R sequence variants are associated with malignant melanoma risk, and most commonly are missense mutations. Few (n=9) truncating mutations have been described in this gene as predisposing to malignant melanoma. In this study, three Jewish individuals were found to harbor an identical truncating MC1R mutation--Y152X: an Ashkenazi patient with two malignant melanomas, a non-Ashkenazi malignant melanoma patient with familial malignant melanoma and her asymptomatic mother. Both malignant melanoma patients carried additional, seemingly pathogenic MC1R variants. Haplotype analysis revealed that all three mutation carriers shared the same haplotype. This sequence variant was previously described in ethnically diverse, non-Jewish individuals and in all likelihood represents an error-prone domain that, in conjunction with other genetic and environmental factors, increases malignant melanoma risk.
黑素皮质素受体1（MC1R）序列变异与恶性黑色素瘤风险相关，且最常见的是错义突变。该基因中作为恶性黑色素瘤易感因素的截短突变很少见（n = 9）。在本研究中，发现三名犹太个体携带相同的截短型MC1R突变——Y152X：一名患有两处恶性黑色素瘤的阿什肯纳兹患者、一名患有家族性恶性黑色素瘤的非阿什肯纳兹恶性黑色素瘤患者及其无症状的母亲。两名恶性黑色素瘤患者均携带其他看似致病的MC1R变异。单倍型分析显示，所有三名突变携带者共享相同的单倍型。该序列变异先前在不同种族的非犹太个体中已有描述，很可能代表一个易出错的结构域，与其他遗传和环境因素共同作用会增加恶性黑色素瘤风险。
