Germline RECQL mutations in high risk Chinese breast cancer patients.

Recently, RECQL was reported as a new breast cancer susceptibility gene. RECQL belongs to the RECQ DNA helicase family which unwinds double strand DNA and involved in the DNA replication stress response, telomere maintenance and DNA repair. RECQL deficient mice cells are prone to spontaneous chromosomal instability and aneuploidy, suggesting a tumor-suppressive role of RECQL in cancer. In this study, RECQL gene mutation screening was performed on 1110 breast cancer patients who were negative for BRCA1, BRCA2, TP53 and PTEN gene mutations and recruited from March 2007 to June 2015 in the Hong Kong Hereditary and High Risk Breast Cancer Program. Four different RECQL pathogenic mutations were identified in six of the 1110 (0.54 %) tested breast cancer patients. The identified mutations include one frame-shift deletion (c.974_977delAAGA), two splicing site mutations (c.394+1G>A, c.867+1G>T) and one nonsense mutation (c.796C>T, p.Gln266Ter). Two of the mutations (c.867+1G>T and p.Gln266Ter) were seen in more than one patients. This study provides the basis for existing of pathogenic RECQL mutations in Southern Chinese breast cancer patients. The significance of rare variants in RECQL gene in the estimation of breast cancer risk warranted further investigation in larger cohort of patients and in other ethnic groups.