Kirsten Rat Sarcoma Mutation in South Indians with Non-Small Lung Cancer

Abstract

Background: Lung cancer is the poster child for advances in molecular oncology with a myriad of targeted therapies in NSCLC (non-small cell lung cancer) management. Kirsten rat sarcoma (KRAS) mutations are routinely isolated in NSCLC and account for a third of NSCLC oncogene driver tumors in Caucasian populations. The mutation is classically notorious to target with most therapies employed in management of KRASmut NSCLC being inhibitors of downstream signaling such as mitogen-activated protein kinase inhibitors (trametinib and selumetinib). There is a lacuna of information regarding prevalence and molecular epidemiology of KRAS mutations in NSCLC from an Indian context. Materials and Methods: The following study is a retrospective analysis of the incidence of KRAS epidemiology in high concentration epidermal growth factor receptor (EGFR) samples at a tertiary care hospital in South India from 2015 to 2017. Samples were selected following histopathological assessment and were subjected to nucleic acid extraction. KRAS mutation testing was performed using real-time polymerase chain reaction to ascertain the molecular epidemiology of KRAS in NSCLC patients. Results: KRAS mutations were observed in 15/44 NSCLC patients (34.09%) with a M:F ratio of 2:1. Majority of the mutations were single mutations, with 3 cases showing double mutations. Codon 12 mutations were observed in 6 cases followed by codon 146 mutations seen in 5 cases. Exon 3 (codon 59 and codon 61) and exon 4 (codon 117 and codon 146) were isolated in 5 and 3 cases, respectively. The current study demonstrated an elevated frequency for KRAS mutations in comparison to Asian cohorts. Conclusion: The advent of directly targeting KRAS inhibitors such as sotorasib (KRAS G12C inhibitor) necessitates KRAS mutation testing and warrants inclusion in the initial molecular workup of NSCLC.