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

Hum Mutat 2019 Aug 24. Epub 2019 Aug 24.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23900DOI Listing
August 2019
5.144 Impact Factor

Publication Analysis

Top Keywords

cell carcinoma
12
renal cancer
12
c1431_1433dupaaa plys477dup
12
renal cell
12
including renal
8
cancer
8
associated cancer
8
cancer including
8
patients renal
8
fumarate hydratase
8
372 patients
8
plys477dup variant
8
renal
6
c1431_1433dupaaa
5
cancer received
4
patients cancer
4
dataset lacking
4
lacking conclusively
4
alteration large
4
received germline
4

References

(Supplied by CrossRef)
Molecular analysis and prenatal diagnosis of human fumarase deficiency
Coughlin E. M. et al.
Molecular Genetics and Metabolism 1998
Molecular and biochemical investigations in fumarase deficiency
Deschauer M. et al.
Molecular Genetics and Metabolism 2006

Ewbank C. et al.
1993
Hysterectomy surveillance in the United States, 1997 through 2005
Merrill R. M. et al.
Medical Science Monitor 2008

Similar Publications