RECQL (RecQ helicase-like; OMIM#600537)是RecQ解旋酶家族成员，在DNA复制、损伤修复等过程发挥重要作用。本课题组前期通过全外显子组测序首次发现RECQL是重要的乳腺癌易感基因，并且发现RECQL低表达的乳腺癌侵袭性强、预后差。目前RECQL的致瘤机制及其临床意义尚不明确。本项目利用CRISPR/Cas9构建RECQL缺陷小鼠模型，拟通过观察小鼠成瘤来验证RECQL缺陷是否有致瘤作用；采用小鼠肿瘤组织高通量测序及小鼠细胞功能试验探索RECQL缺陷的致瘤机制；开展小鼠细胞药敏实验探索RECQL缺陷是否是肿瘤靶向药物PARP (poly ADP-ribose polymerases) 抑制剂的治疗靶点。本研究有利于揭示RECQL缺陷的致瘤机制，为RECQL突变健康携带者加强监测和预防奠定基础，为携带RECQL突变乳腺癌患者的靶向治疗提供实验依据。

RECQL (RecQ helicase-like; OMIM#600537) is a member of the RecQ helicase family and plays an important role in DNA replication and repair. Our previous study was the first to report that RECQL is a breast cancer susceptibility gene by whole exome sequencing and found that low expression of RECQL was associated with aggressive phenotype and poor prognosis in breast cancer. However, the tumorigenic mechanism of RECQL deficiency is still unclear. This project plans to construct a RECQL-deficient mouse model by CRISPR/Cas9 method, we aim to verify the tumorigenic effect of RECQL deficiency by observing the tumorigenesis of mouse models, and to explore the tumorigenic mechanism by performing high-throughput sequencing on mouse tumor tissue and by function assays on mouse cells, and to explore the synthetic lethal effect between RECQL deficiency and PARP (poly ADP-ribose polymerases) inhibitors in vitro. This study is helpful to reveal the tumorigenic mechanism of RECQL deficiency, and to provide evidence for enhanced surveillance and preventive intervention in unaffected RECQL mutation carriers, and to provide experimental basis for targeted therapy of breast cancer patients carrying RECQL mutation.