Concomitant genomic alterations in KRAS mutant advanced lung adenocarcinoma.
Adenocarcinoma of Lung
/ drug therapy
Biomarkers, Tumor
/ genetics
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cohort Studies
Follow-Up Studies
Genomics
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms
/ drug therapy
Mutation
Platinum
/ therapeutic use
Prognosis
Proto-Oncogene Proteins p21(ras)
/ genetics
Survival Rate
Co-alterations
KRAS
Next generation sequencing (NGS)
Non-small cell lung cancer (NSCLC)
Targeted therapies
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
20
09
2019
revised:
29
11
2019
accepted:
03
12
2019
pubmed:
22
12
2019
medline:
7
4
2021
entrez:
22
12
2019
Statut:
ppublish
Résumé
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. 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 (KRASm) and in 32 KRAS wild-type (KRASwt). TP53 was the most frequent additional alteration found in both cohorts. Interestingly, TP53 mutations were more frequent in KRASwt than in KRASm patients (80 % vs. 34 %; p < 0.05) as well as STK11 mutations (17 % vs 8 %, p=NS). FGFR3 mutations were only found concomitantly with KRASm (11 %). No genomic co-alteration had an impact on overall survival within the KRASm patients treated with chemotherapy. KRAS mutated lung adenocarcinoma is a heterogeneous entity and comprehensive characterization of co-alterations using NGS may lead to more accurate patient stratification.
Identifiants
pubmed: 31862576
pii: S0169-5002(19)30756-1
doi: 10.1016/j.lungcan.2019.12.003
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
KRAS protein, human
0
Platinum
49DFR088MY
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
42-45Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.