Prospective targeted next generation sequencing of EGFR pathway genes in tumors of Filipino Young-Onset Colorectal Cancer Patients

Advances in next generation sequencing (NGS) technologies have allowed us to gain remarkable insights on the colorectal cancer (CRC) genome, expanding our view of the mutational landscape of CRC throughout the progression of the disease. In the Philippines, incidence of CRC in the young (YO-CRC) has been noted at 17%, which is substantially higher than the global average of 2.5-8% of all CRC cases. Based on related studies elsewhere, the mutational signature of this subset of patients is different from that of late-onset cases and there also appears to be differences between ethnic groups. In a prospective NGS study of tumor samples from Filipino YO-CRC patients, many novel and uncharted mutations in EGFR pathway genes were identified as well as potential miRSNPs in 3'UTRs. Intra-tumoral and intertumoral heterogeneity across patients were also apparent. Detailed characterization of these uncharted mutations including mechanistic studies on downstream effector engagement, may reveal differential oncogenic phenotypes that can aid prognostication.