Germline mutations in early-onset or hereditary breast cancer from the Middle East.

Abstract

20 Background: Breast cancer is the most common cancer affecting women of Middle Eastern origin. Epidemiologically, breast cancer in the Middle East clusters in families and usually affects women a decade younger than Western women. This dilemma is compounded by the lack of curated databases and ambitious studies that address the roles genetic or genomic may play in breast cancer. Methods: We have exome sequenced 60 Middle Eastern women with moderate and strong family history of cancer or young women without significant family history of cancer. DNA extracted from peripheral blood of patients and matching normal Middle Eastern women without history of familial or sporadic cancers, were subjected to whole-exome sequencing using the HiSeq 2500 Illumina platform and MLPA to map major breast cancer–activating genetic defects. Results: Several novel BRCA1/2 mutations were identified in the minority of these women. However, other complex mutations in non-BRCA1/2 genes appear to play a more subtle role in breast cancer in the Middle Eastern women. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. Conclusions: BRCA1/2 gene mutations are not a significant cause of heritable cancers in the Middle East. The region may benefit from a well-curated region-specific database accessible to clinicians and scientists where clinical and variants information can be deposited from all over the Middle East.