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. 2020 Jan;41(1):103-109.
doi: 10.1002/humu.23900. Epub 2019 Sep 3.

Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma

Liying Zhang  1 , Michael F Walsh  2   3 , Sowmya Jairam  1 , Diana Mandelker  1 , Yi Zhong  1   4 , Yelena Kemel  4 , Ying-Bei Chen  1 , David Musheyev  5 , Ahmet Zehir  1 , Gowtham Jayakumaran  1 , Edyta Brzostowski  1 , Ozge Birsoy  1 , Ciyu Yang  1 , Yirong Li  1 , Joshua Somar  1 , Deborah DeLair  6 , Nisha Pradhan  7 , Michael F Berger  1 , Karen Cadoo  3   8 , Maria I Carlo  3   8 , Mark E Robson  3   8 , Zsofia K Stadler  3   8 , Christine A Iacobuzio-Donahue  1   9 , Vijai Joseph  3   8 , Kenneth Offit  3   8
Affiliations

Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma

Liying Zhang et al. Hum Mutat. 2020 Jan.

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.

Keywords: FH; FH c.1431_1433dupAAA; FH deficiency; FH p.Lys477dup; HLRCC.

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Conflict of interest statement

Conflict of Interest

Dr. Zhang: Honoraria (Future Technology Research LLC, BGI, Illumina); Honoraria and Travel and accommodation expenses: Roche Diagnostics Asia Pacific. Family member has a leadership position and ownership interest of Shanghai Genome Center. Dr. Cadoo: Institutional support for therapeutic trials (AstraZeneca and Syndax Pharmaceuticals); Travel and accommodation: AstraZeneca.Dr. Carlo: Advisory role (Pfizer). Dr. Robson: Honoraria (Advisory): AstraZeneca; Consulting or Advisory: AstraZeneca, Daiichi-Sanyo (uncompensated), McKesson, Merck (uncompensated); Research Funding: AbbVie (institution); AstraZeneca (Institution); Invitae (Institution, in-kind); Medivation (Institution); Myriad (Institution, in-kind); Pfizer (institution); Tesaro (institution); Travel, Accommodation, Expenses: AstraZeneca; Other transfer of value: Pfizer (editorial services). All other authors declare no conflict of interest

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