Incidence of Microsatellite Instability, Mutational Burden, and Actionable Alterations in Genes of Patients with Metastatic Colorectal Carcinoma: A Study from a Tertiary Care Hospital in India

Abstract

Background and objective: Tumor mutational burden (TMB) and microsatellite instability (MSI) are predictive clinical markers of responses to immunotherapy in a wide range of advanced cancers, including colorectal cancers. The data about TMB and MSI in Indian patients is scarce. Hence, assessed the incidence of MSI, TMB, and actionable alterations in genes of patients with metastatic colorectal carcinoma. Methods: A single centre, observational, prospective study in newly diagnosed patients (n=60) with colorectal carcinoma were assessed for MSI incidence, mutational burden, and actionable alterations in genes. Results: The TMB ranged between 5.08 and 2391 mutations per megabase, and 12 (20%) had low TMB, 12 (20%) intermediate TMB and 36 (60%) high TMB. The TMB was high in right-sided than left-sided cancer (100% vs. 47%). Three or more two, and one genomic alteration were observed in 26 (44%), 20 (33%), and (20%) patients, respectively. Gene fusion was absent in all 60 patients. Gene mutations were predominant in the left-sided than right-sided but statistically insignificant (p=0.7). APC, TP53, and BRCA2 gene mutations were evident in 46, 28, and 22 patients, respectively. Wild KRAS/NRAS gene alterations were evident in all metastatic cancers (n=22) presented at baseline. There was no significant correlation between the genomic alterations and age, sex, histology, or tumor differentiation. Conclusion: This study highlights the importance of detecting genomic mutations at the earliest. Genomic mutations should form the basis for customizing and exploring newer targeted therapy against the most common genomic alteration like APC, TP53, and RAS mutations to improve outcomes.

Keywords

• sarcopenia, sarcopenic obesity, guidelines, secondary sarcopenia, south asian, body composition