Genomic Alterations of KRAS and NRAS in B&H Colorectal and Non-small Cell Lung Cancer Patients

Abstract

Non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) are two leading neoplasms in population of Bosnian cancer patients and a leading cause of death. RAS family of genes, in particular KRAS gene, is one of the most frequently mutated oncogene in these cancer types. This paper reports diagnostic samples from 36 CRC and 14 NSCLC Bosnian patients that were analyzed by next generation sequencing (NGS). Based on Ion AmpliSeq technology, NGS enabled molecular characterization of a panel of 22 hotspot regions of genes known to be involved in pathogenesis of NSCLC and CRC. We identified 33.3% of CRC patients harboring KRAS mutations and 11.1% patients harboring NRAS mutations. In NSCLC group, we identified 35.7% of KRAS-mutant patients. None of the NSCLC patients carried NRAS mutation. We found that CRC patients harbored 8 distinctive KRAS mutation subtypes, most of which were pathogenic. KRAS G13D was the most frequently occurring KRAS mutation subtype (33.3%) in CRC. 2 subtypes of NRAS mutations were detected, one of which was a well-documented pathogenic mutation. In NSCLC patients, we detected 3 KRAS mutant subgroups. KRAS G12C mutant was the most frequently detected KRAS mutation subtype in NSCLC patients (80%). Mean number of co-occurring aberrations per cancer type was 6.75 and 11 for CRC and NSCLC, respectively. Two most frequently co-occurring pathogenic aberrations were found in TP53 and PIK3CA genes. Thus, RAS-mutants in the population of B&H cancer patients are highly heterogeneous and distinctive molecular profiles have potentially different implications in cancer-associated pathways and therapeutic significance indicating the need for further investigation of KRAS subtype as a potent biomarker.