Concomitant genomic alterations in KRAS mutant advanced lung adenocarcinoma. (February 2020)

• Record Type: Journal Article
• Authors: Gibert, Joan; Clavé, Sergi; Hardy-Werbin, Max; Taus, Álvaro; Rocha, Pedro; Longarón, Raquel; Piquer, Gabriel; Chaib, Imane; Carcereny, Enric; Morán, Teresa; Salido, Marta; Dalmases, Alba; Bellosillo, Beatriz; Arriola, Edurne
• Is Part Of: Lung cancer. Volume 140(2020)
• Page Start: 42
• Page End: 45
• Publication Date: 2020-02
• Subjects: Non-small cell lung cancer (NSCLC) -- Next generation sequencing (NGS) -- Targeted therapies -- KRAS -- Co-alterations; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.12.003
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: KRAS mutant lung adenocarcinoma harbors multiple concurrent genomic alterations. The most frequent coalterations were TP53 and STK11 point mutations. Coalterations did not impact in outcome of patients treated with chemotherapy. Abstract: Objectives: KRAS mutations are one of the most prevalent alterations in non-small cell lung cancer. However, patients with this driver alteration present heterogeneous clinical outcomes. In this study, we have explored the potential clinical impact of coexisting alterations in this subset of patients. Materials and methods: Samples from a cohort of 69 lung adenocarcinoma patients homogenously treated with platinum doublet as first-line therapy were evaluated using targeted next generation sequencing (NGS). Mutations and copy number alterations were assessed in 37 advanced KRAS -mutant ( KRAS m) and in 32 KRAS wild-type ( KRAS wt). Results: TP53 was the most frequent additional alteration found in both cohorts. Interestingly, TP53 mutations were more frequent in KRAS wt than in KRAS m patients (80 % vs. 34 %; p < 0.05) as well as STK11 mutations (17 % vs 8 %, p =NS). FGFR3 mutations were only found concomitantly with KRAS m (11 %). No genomic co-alteration had an impact on overall survival within the KRAS m patients treated with chemotherapy. Conclusions: KRAS mutated lung adenocarcinoma is a heterogeneous entity and comprehensive characterization of co-alterations using NGS may lead to more accurate patient stratification.