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Nat Genet. 2015 Jun;47(6):643-6. doi: 10.1038/ng.3284. Epub 2015 Apr 27.

Germline RECQL mutations are associated with breast cancer susceptibility.

Author information

1
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
2
1] Department of Human Genetics, McGill University, Montréal, Québec, Canada. [2] McGill University and Génome Québec Innovation Centre, Montréal, Québec, Canada.
3
1] Department of Human Genetics, McGill University, Montréal, Québec, Canada. [2] Department of Medical Genetics, Lady Davis Institute, Jewish General Hospital, Montréal, Québec, Canada.
4
Unité de Recherche en Génétique Humaine et Moléculaire, Axe Santé des Populations et Pratiques Optimales en Santé, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
5
Department of Human Genetics, McGill University, Montréal, Québec, Canada.
6
1] Department of Human Genetics, McGill University, Montréal, Québec, Canada. [2] Department of Medical Genetics, McGill University, Montréal, Québec, Canada. [3] Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
7
Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada.
8
Tadeusz Koszarowski Regional Oncology Center, Opole, Poland.
9
1] Unité de Recherche en Génétique Humaine et Moléculaire, Axe Santé des Populations et Pratiques Optimales en Santé, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada. [2] Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, Québec, Canada.
10
1] Department of Human Genetics, McGill University, Montréal, Québec, Canada. [2] Department of Medical Genetics, Lady Davis Institute, Jewish General Hospital, Montréal, Québec, Canada. [3] Department of Medical Genetics, McGill University, Montréal, Québec, Canada. [4] Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. [5] Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Québec, Canada.
11
1] Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Abstract

Several moderate- and high-risk breast cancer susceptibility genes have been discovered, but more are likely to exist. To discover new breast cancer susceptibility genes, we used 2 populations (from Poland and Quebec, Canada) and applied whole-exome sequencing in a discovery phase (n = 195), followed by validation. We identified rare recurrent RECQL mutations in each population. In Quebec, 7 of 1,013 higher-risk breast cancer cases and 1 of 7,136 newborns carried the c.634C>T (p.Arg215*) variant (P = 0.00004). In Poland, 30 of 13,136 unselected breast cancer cases and 2 of 4,702 controls carried the c.1667_1667+3delAGTA (p.K555delinsMYKLIHYSFR) variant (P = 0.008). RECQL is implicated in resolving stalled DNA replication forks to prevent double-stranded DNA (dsDNA) breaks. This function is related to that of other known breast cancer susceptibility genes, many of which are involved in repairing dsDNA breaks. We conclude that RECQL is a breast cancer susceptibility gene.

PMID:
25915596
DOI:
10.1038/ng.3284
[Indexed for MEDLINE]

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