Genomic profiling of early-onset and hereditary breast cancer.

Abstract

30 Background: Worldwide, breast cancer is the most common cancer in women. Susceptibility is thought to be polygenic and the risk tends to increase in women with positive family history of breast cancer. Methods: We proposed an ambitious Middle Eastern-based study that entailed exome sequencing of approximately 50 women from the Middle East (M.E) with moderate family history of any cancer. DNA from tumor samples with matching lymphocytes from the same subjects and 50 normal Middle Eastern women without history of familial or sporadic cancers in the family, were subjected to whole-exome sequencing on the HiSeq 1000/2000 Illumina platforms to map major breast cancer–activating genetic defects. Results: Several unique to the M.E region and novel germline mutations in non-BRCA1/2 genes were identified in this cohort. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. More importantly, the breast cancers showed interesting copy number and mutations variants that may aid our understanding of breast cancer initiations. Conclusions: The M.E. breat cancer may be caused by a unique set of germline variants and that the M.E breast cancers may represent an entity that may aid in our understanding of this common disease.