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Updated: Oct 15, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
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.
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.
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.
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