| Literature DB >> 31444830 |
Liying Zhang1, Michael F Walsh2,3, Sowmya Jairam1, Diana Mandelker1, Yi Zhong1,4, Yelena Kemel4, Ying-Bei Chen1, David Musheyev5, Ahmet Zehir1, Gowtham Jayakumaran1, Edyta Brzostowski1, Ozge Birsoy1, Ciyu Yang1, Yirong Li1, Joshua Somar1, Deborah DeLair6, Nisha Pradhan7, Michael F Berger1, Karen Cadoo3,8, Maria I Carlo3,8, Mark E Robson3,8, Zsofia K Stadler3,8, Christine A Iacobuzio-Donahue1,9, Vijai Joseph3,8, Kenneth Offit3,8.
Abstract
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.Entities:
Keywords: FH; FH c.1431_1433dupAAA; FH deficiency; FH p.Lys477dup; HLRCC
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Year: 2019 PMID： 31444830 PMCID： PMC6930334 DOI： 10.1002/humu.23900
Source DB: PubMed Journal: Hum Mutat ISSN： 1059-7794 Impact factor: 4.878