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Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma
Author(s) -
Zhang Liying,
Walsh Michael F.,
Jairam Sowmya,
Mandelker Diana,
Zhong Yi,
Kemel Yelena,
Chen YingBei,
Musheyev David,
Zehir Ahmet,
Jayakumaran Gowtham,
Brzostowski Edyta,
Birsoy Ozge,
Yang Ciyu,
Li Yirong,
Somar Joshua,
DeLair Deborah,
Pradhan Nisha,
Berger Michael F.,
Cadoo Karen,
Carlo Maria I.,
Robson Mark E.,
Stadler Zsofia K.,
IacobuzioDonahue Christine A.,
Joseph Vijai,
Offit Kenneth
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23900
Subject(s) - cancer , biology , germline , renal cell carcinoma , cancer syndrome , kidney cancer , germline mutation , fumarase , leiomyomatosis , cancer research , carcinoma , mutation , genetics , medicine , pathology , gene , leiomyoma
Fumarate hydratase ( FH ) mutations underpin the autosomal recessive syndrome. FH deficiency and the autosomal dominant syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH c.1431_1433dupAAA (p.Lys477dup) genomic alteration has been conclusively shown to contribute to FH deficiency when occurring with another FH germline alteration. However, a sufficiently large dataset has been lacking to conclusively determine its clinical significance to cancer predisposition in the heterozygous state. We reviewed a series of 7,571 patients with cancer who received germline results through MSK‐IMPACT testing at the Memorial Sloan Kettering Cancer Center. The FH c.1431_1433dupAAA (p.Lys477dup) variant was detected in 24 individuals, none of whom was affected with renal cancer. Eleven of the 372 patients with renal cancer were identified to carried pathogenic FH variants associated with HLRCC. None of these 372 patients with renal cancer carried the FH c.1431_1433dupAAA variant. Our data indicate the FH c.1431_1433dupAAA is not associated with cancer including renal cell carcinoma.