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Cancer is a disease that comprises an acquired (somatic) mutations, where the accumulation of genetic mutations leads to the acquisition of cancer-related traits such as the ability of cells to hyperproliferate and invade; and a heritable component where germline susceptibility alleles of varying penetrance confer cancer predisposition.. Frequently, the same genes are also commonly mutated in non-heritable (sporadic) tumors (e.g. TP53, BRCA1, APC). For epithelial ovarian cancer (EOC), WGS analysis of >500 ovarian tumors generated by ourselves and others, finds on average ~10,000 somatic single nucleotide mutations per tumor, with non-coding variants representing more than 98% of all somatically acquired mutations.
We are currently using several experimental approaches to answer the question whether non-coding genetic variation, where both somatic and germline disease associated variants (DAVs) co-localize within non-coding regulatory elements to impact the expression of target genes and gene expression networks that are critical for cancer initiation, development and clinical outcomes.