Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients.

Veronica Aran,Carlos Augusto Moreira De Sousa,Mariano Zalis,Bruno L Ferrari,Tatiane Montella,Carlos Gil Ferreira

doi:10.3390/medicina57101039

Abstract

Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. Materials and Methods: This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. Results: The results showed a prevalence of male (N = 63; 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. Conclusions: This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted.

Highlights

Lung cancer kills approximately 1.8 million people worldwide every year, affecting more males than females [1]
Data from 121 patients were analyzed to evaluate the incidence of KRAS G12C mutations in advanced lung adenocarcinoma patients and correlated, when possible, to clinicopathological characteristics such as sex
Six patients showed inconclusive results, whereas 115 had valid samples, which were analyzed for the incidence of KRAS mutations

Summary

Introduction

Lung cancer kills approximately 1.8 million people worldwide every year, affecting more males than females [1]. The most frequently found histology subtype is non-small cell lung cancer (NSCLC), corresponding to 80% of tumors and subdivided into adenocarcinoma (35–40%), squamous cell carcinoma (25–30%), and large cell carcinoma (10–15%) [2]. The most common driving mutations observed in NSCLC correspond to the ones found in epidermal growth factor receptor (EGFR), KRAS, human epidermal growth factor receptor. 30% of lung adenocarcinomas and in approximately 5% of the squamous-cell carcinoma subtype with a higher incidence occurring in current or former smokers than in never smokers [3]. The KRAS mutation frequencies in NSCLC vary according to different ethnic populations, ranging from 15–32% [4].

Objectives

Methods

Results

Discussion

Conclusion