Site specific genetic differences in colorectal cancer via Next-Generation-Sequencing using a multigene panel.

ABSTRACT

AIM: Next-generation sequencing (NGS) has been proposed as a comprehensive and efficient genomic profiling tool to guide personalized therapy for colorectal cancer. This study aimed to review the site-specific difference and the potential benefits of actionable mutation panel for colorectal cancer in relation to the clinicopathological features. MATERIAL AND METHODS: One hundred and six patients who underwent colorectal surgery with curative or palliative intent for histopathologically confirmed carcinoma between June 2016 and June 2018 were identified from a prospectively maintained database. Formalin-fixed, paraffin-embedded tumor tissues were analyzed for actionable variants in 11 genes via NGS (EGFR, ALK, KRAS, NRAS, KIT, BRAF, PDGFRA, ERBB2, ERBB3, ESR1, and RAF1). RESULTS: Most of the primary tumors were in the rectum (49 patients; 46.2%) followed by the right colon (32 patients; 30.1%) and left colon (25 patients; 23.5%), respectively. Of sequenced cases, 43 KRAS mutations, 7 EGFR mutations, 6 NRAS mutations, 6 BRAF mutations, 3 KIT mutations, 1 ERBB2 mutation, 1 PDGFRA mutation, and 1 RAF1 mutation were identified in 106 patients. The frequency of mutations is mostly concentrated on the right colon group. The highest drug resistance observed in all patients was against Cetuximab and Panitumumab, and the highest drug resistance was found in the right colon group (53.1%). CONCLUSIONS: The utility of actionable multigene panel revealed the value of a well-designed next-generation sequencing workflow in the practical use of clinical outcomes via the prediction of responsiveness to therapeutic agents or indications for novel treatment modalities in addition to prognosis estimate. KEY WORDS Colorectal Cancer, Drug Resistance, Next-Generation Sequencing.