Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome

Molecular Genetics & Genomic Medicine

Anna Maio¹  Maria I. Carlo¹  Kelsey E. Breen¹  Ozge Ceyhan‐Birsoy²  Ying‐Bei Chen²  Diana Mandelker²  Liying Zhang³  Yelena Kemel⁴ 

[1] Department of Medicine Memorial Sloan Kettering Cancer Center New York City NY USA;Department of Pathology Memorial Sloan Kettering Cancer Center New York City NY USA;Department of Pathology and Laboratory Medicine University of California Los Angeles CA USA;Niehaus Center for Inherited Cancer Genomics Sloan Kettering InstituteMemorial Sloan Kettering Cancer Center New York City NY USA;

关键词: carcinoma;    fumarate hydratase;    leiomyomatosis;    mutation;    renal cell;   

DOI  :  10.1002/mgg3.1293

来源: DOAJ

【 摘 要 】

Abstract Background Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. Methods About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor‐normal sequencing under an IRB approved protocol. Results We report two unrelated individuals with early onset kidney cancer who both carried the c.914C > T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas. Conclusion This combination of evidence suggests that the FH c.914C > T (p.Phe305Ser) is pathogenic for HLRCC.

【 授权许可】

Unknown