扩展E318K（c.952G > A）MITF种系突变携带者的表型：病例系列及文献综述
Expanding the phenotype of E318K (c.952G > A) MITF germline mutation carriers: case series and review of the literature.
作者信息
Oliveira Leandro Jonata Carvalho, Gongora Aline Bobato Lara, Lima Fabiola Ambrosio Silveira, Canedo Felipe Sales Nogueira Amorim, Quirino Carla Vanessa, Pisani Janina Pontes, Achatz Maria Isabel, Rossi Benedito Mauro
机构信息
Serviço de Oncogenética - Centro de Oncologia Hospital Sírio-Libanês, Rua Dona Adma Jafet, 91, 01308-050, São Paulo, Brazil.
出版信息
Hered Cancer Clin Pract. 2021 Jul 21;19(1):32. doi: 10.1186/s13053-021-00189-8.
BACKGROUND
The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma.
CASE PRESENTATION
We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives.
CONCLUSIONS
Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.
背景
小眼畸形相关转录因子基因（MITF）属于MYC超基因家族，在黑素细胞的稳态中起重要作用。携带MITF种系致病变异的个体患癌症的风险增加，最常见的是黑色素瘤和肾细胞癌。
病例报告
我们描述了一组十名携带相同的MITF c.952G＞A（p.Glu 318Lys）或p.E318K种系致病变异的个体。六名携带者发生了至少一种恶性肿瘤（4例乳腺癌；1例宫颈癌；1例结肠癌；1例黑色素瘤；1例卵巢/输卵管癌）。在这些个体及其亲属中发现了显著的表型异质性。总体而言，乳腺癌是该病例系列中观察到的最常见恶性肿瘤，在先证者及其亲属中描述的60例（21.67%）总癌症病例中有13例发生乳腺癌。
结论
我们的回顾性分析数据提出了MITF p.E318K致病变异可能与乳腺癌风险增加相关的假说。
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