Expanding the phenotype of E318K (c.952G > A) MITF germline mutation carriers: case series and review of the literature

Hereditary Cancer in Clinical Practice

Carla Vanessa Quirino¹  Maria Isabel Achatz¹  Fabiola Ambrosio Silveira Lima¹  Felipe Sales Nogueira Amorim Canedo¹  Leandro Jonata Carvalho Oliveira¹  Benedito Mauro Rossi¹  Aline Bobato Lara Gongora¹  Janina Pontes Pisani¹ 

[1] Serviço de Oncogenética – Centro de Oncologia Hospital Sírio-Libanês, Rua Dona Adma Jafet, 91, 01308-050, São Paulo, Brazil;

关键词: MITF;    c.952G > A;    p.E318K;    Hereditary cancer;    Multigene sequencing panel;    Breast cancer;   

DOI  :  10.1186/s13053-021-00189-8

来源: Springer

【 摘 要 】

BackgroundThe 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 presentationWe 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.ConclusionsOur retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.

【 授权许可】

CC BY