Identifying and characterizing novel genetic risk factors for BRCA1/2 negative breast cancers is highly relevant for early diagnosis and development of a management plan. Mutations in a number of DNA repair genes have been associated with genomic instability and development of breast and various other cancers. Whole exome sequencing efforts by 2 groups have led to the discovery in distinct populations of multiple breast cancer susceptibility mutations in RECQL, a gene that encodes a DNA helicase involved in homologous recombination repair and response to replication stress. RECQL pathogenic mutations were identified that truncated or disrupted the RECQL protein or introduced missense mutations in its helicase domain. RECQL mutations may serve as a useful biomarker for breast cancer. Targeting RECQL associated tumors with novel DNA repair inhibitors may provide a new strategy for anti-cancer therapy.
Keywords: DNA damage; DNA repair; RECQ1; RECQL; breast cancer; genomic instability; helicase.