Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
1] Department of Human Genetics, McGill University, Montréal, Québec, Canada. [2] McGill University and Génome Québec Innovation Centre, Montréal, Québec, Canada.
Nat Genet. 2015 Jun;47(6):643-6. doi: 10.1038/ng.3284. Epub 2015 Apr 27.
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.
已经发现了一些中高危乳腺癌易感基因，但可能还有更多的基因存在。为了发现新的乳腺癌易感基因，我们使用了两个群体（来自波兰和加拿大魁北克），在发现阶段（n=195）进行了全外显子组测序，然后进行了验证。我们在每个群体中都发现了罕见的 RECQL 突变的反复出现。在魁北克，1013 名高危乳腺癌病例中有 7 名和 7136 名新生儿中有 1 名携带 c.634C>T（p.Arg215*）变异（P=0.00004）。在波兰，在 13136 名未经选择的乳腺癌病例中有 30 名和在 4702 名对照中有 2 名携带 c.1667_1667+3delAGTA（p.K555delinsMYKLIHYSFR）变异（P=0.008）。RECQL 参与解决停滞的 DNA 复制叉，以防止双链 DNA（dsDNA）断裂。该功能与其他已知的乳腺癌易感基因的功能相关，其中许多基因参与修复 dsDNA 断裂。我们得出结论，RECQL 是一个乳腺癌易感基因。
