SLX4 is a DNA repair protein that serves as a docking platform for three structure-specific endonucleases. Recent studies have reported mutations in SLX4 in a new subtype of Fanconi Anemia (FA-P). Monoallelic defects in several Fanconi Anemia genes are known to confer susceptibility to breast and ovarian cancer. Therefore, we resequenced the entire SLX4 coding region in 739 (288 Ashkenazi Jewish and 480 Non-Ashkenazi Jewish) breast cancer patients with 3 or more family members affected by breast cancer and no known BRCA1/BRCA2 mutations, to determine if SLX4 is involved in breast cancer susceptibility. We found a novel nonsense (p.W823*) mutation in one patient. We are sequencing the gene in the breast tumor from the patient to determine the status of the wild-type allele. In addition we also found 8 novel, 33 rare (MAF<1%), and 3 common (MAF> 0.5) missense variants, of which 12 (5 novel and 10 rare) are predicted as damaging by Polyphen2. Functional analysis of these missense mutations is being performed to determine their role in the pathogenicity of the SLX4 gene. Acknowlegements- This project was funded by The Starr Cancer Consotium (Agata Smorgorzewska and Kenneth Offit), The Rita Allen Foundation Scholars Program Grant (Agata Smorgorzewska) and Burroughs Wellcome Fund Career Award for Medical Scientists (Agata Smorgorzewska). We would like to thank the Geoffrey Beene Translational Oncology and Diagnostic Molecular Genetics laboratories for their help with the study.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2600. doi:1538-7445.AM2012-2600