title: Mutation analysis and characterization of HSD17B2 sequence variants in breast cancer cases from French Canadian families with high risk of breast and ovarian cancer.
abstract: Estrogen exposure is a risk factor for breast cancer. Given that HSD17B2 gene encodes an enzyme that catalyses estradiol inactivation, it appears as a good candidate breast cancer susceptibility gene. This study was designed to screen for HSD17B2 germline mutations potentially involved in breast cancer predisposition. Our re-sequencing analysis did not identify any deleterious germline mutations, and therefore mutations in HSD17B2 do not explain the clustering of breast cancer cases in non-BRCA1/2 high-risk French Canadian families. However, six sequence variants were identified, including two novel missense variants. Expression assays revealed that p.Ala111Asp and p.Gly160Arg did not alter the catalytic properties of 17beta-hydroxysteroid dehydrogenase type 2 enzyme, although p.Ala111Asp appears to affect protein stability resulting in significant decreases in the protein levels, providing valuable information on structure-function relationship.
authors: Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Québec and Laval University, Quebec G1V 4G2, Canada.
authors: Marie
authors: M
authors: Plourde
authors: Caroline
authors: C
authors: Manhes
authors: Gilles
authors: G
authors: Leblanc
authors: Francine
authors: F
authors: Durocher
authors: Martine
authors: M
authors: Dumont
authors: Olga
authors: O
authors: Sinilnikova
authors: Jacques
authors: J
authors: Simard
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004960:Estradiol Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D005190:Family; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011792:Quebec; D012307:Risk Factors; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human