title: Mutations in RECQL Gene Are Associated with Predisposition to Breast Cancer.
abstract: The genetic cause for approximately 80% of familial breast cancer patients is unknown. Here, by sequencing the entire exomes of nine early-onset familial breast cancer patients without BRCA1/2 mutations (diagnosed with breast cancer at or before the age of 35) we found that two index cases carried a potentially deleterious mutation in the RECQL gene (RecQ helicase-like; chr12p12). Recent studies suggested that RECQL is involved in DNA double-strand break repair and it plays an important role in the maintenance of genomic stability. Therefore, we further screened the RECQL gene in an additional 439 unrelated familial breast cancer patients. In total, we found three nonsense mutations leading to a truncated protein of RECQL (p.L128X, p.W172X, and p.Q266X), one mutation affecting mRNA splicing (c.395-2A>G), and five missense mutations disrupting the helicase activity of RECQL (p.A195S, p.R215Q, p.R455C, p.M458K, and p.T562I), as evaluated through an in vitro helicase assay. Taken together, 9 out of 448 BRCA-negative familial breast cancer patients carried a pathogenic mutation of the RECQL gene compared with one of the 1,588 controls (P = 9.14×10-6). Our findings suggest that RECQL is a potential breast cancer susceptibility gene and that mutations in this gene contribute to familial breast cancer development.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, the People's Republic of China.
authors.forename: Yisui
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ouyang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Tie
authors.initials: T
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Benyao
authors.initials: B
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, the People's Republic of China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing, the People's Republic of China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D003001:Cloning, Molecular; D019295:Computational Biology; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D042822:Genomic Instability; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012326:RNA Splicing; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: C506725:RECQL protein, human; D053484:RecQ Helicases