Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients

Veronica Aran1, Mariano Zalis2, Tatiane Montella3

  • 1Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro 20231-092, Brazil.

Insights

Ras (Rat sarcoma) mutations are common in cancer, particularly KRAS in lung cancer. This study found KRAS mutations in 20.86% of advanced lung adenocarcinoma patients, with some rare co-occurring mutations also present.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ras (Rat sarcoma) proteins are key signaling molecules, and their gain-of-function mutations are implicated in approximately 30% of human cancers.
  • KRAS is the most frequently mutated isoform within the Ras family, with alterations observed in various cancer types, including lung cancer.
  • Non-small cell lung adenocarcinoma (NSCLC) is a major type of lung cancer where KRAS mutations are frequently observed.

Purpose of the Study:

  • To determine the incidence of KRAS mutations in advanced non-small cell lung adenocarcinoma (NSCLC) patients.
  • To identify concomitant mutations occurring alongside KRAS mutations in these patients.
  • To explore potential correlations between KRAS mutational status, mutation type, and clinicopathological characteristics, including sex.

Main Methods:

  • Retrospective analysis of genomic DNA extracted from paraffin-embedded tumor tissues of 121 Brazilian advanced NSCLC patients.
  • Next-Generation Sequencing (NGS) was employed to evaluate the incidence of KRAS mutations and co-occurring mutations.
  • Statistical analyses were conducted to assess mutation prevalence and associations with sex.

Main Results:

  • Mutant KRAS was identified in 20.86% (24/115) of the analyzed samples.
  • A prevalence of male (54.8%) compared to female (45.2%) patients was observed.
  • Notably, 33.3% of samples with mutant KRAS also exhibited other simultaneous mutations.

Conclusions:

  • The study identified the presence of KRAS mutations and rare concomitant mutations in advanced lung adenocarcinoma.
  • These genomic alterations may have implications for patient prognosis and response to therapy.
  • Further research is warranted to elucidate the clinical significance of these findings.