Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma.
Adult
Aged
Alleles
Amino Acid Substitution
Carcinoma, Renal Cell
/ genetics
Female
Fumarate Hydratase
/ deficiency
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Genetic Variation
Genotype
Germ-Line Mutation
Humans
Kidney Neoplasms
/ genetics
Leiomyomatosis
/ genetics
Male
Middle Aged
Neoplastic Syndromes, Hereditary
/ genetics
Skin Neoplasms
/ genetics
Uterine Neoplasms
/ genetics
FH
FH c.1431_1433dupAAA
FH deficiency
FH p.Lys477dup
HLRCC
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
23
03
2019
revised:
13
08
2019
accepted:
19
08
2019
pubmed:
25
8
2019
medline:
20
5
2021
entrez:
25
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31444830
doi: 10.1002/humu.23900
pmc: PMC6930334
mid: NIHMS1047754
doi:
Substances chimiques
Fumarate Hydratase
EC 4.2.1.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
103-109Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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