Young Adult CRC Exome

Although colorectal cancer (CRC) remains the second leading cause of death from cancer in the United States, overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been and continues to be, a steady increase in the incidence of CRC in individuals under 50 years of age. Early age of onset is a hallmark of hereditary syndromes that contribute disproportionately to early onset CRC (EOCRC). These include microsatellite instability high (MSI+) tumors arising in patients with Lynch Syndrome. However, the majority of EOCRCs are not associated with familial syndromes or an MSI+ genotype. Comprehensive genomic profiling has provided the basis of improved more personalized treatments for older CRC patients. However, to date similar profiling of EOCRC has been limited. Thus, relative to CRCs in older patients less is known about the basis of sporadic EOCRC. To define the genomic landscape of EOCRC we used DNA content flow sorting to isolate diploid and aneuploid tumor fractions from 21 non-hereditary cases. We then generated whole exome mutational profiles for each case and whole genome copy number, telomere length, and EGFR immunohistochemistry (IHC) analyses on subsets of samples. Our data are a unique description of recurring features of EOCRC including signaling pathways targeted by genomic lesions and mutational signatures reflecting processes operative during their natural history.