Tracking longitudinal genetic changes of circulating tumor DNA (ctDNA) in advanced Lung adenocarcinoma treated with chemotherapy.
Adenocarcinoma of Lung
/ blood
Adult
Aged
Circulating Tumor DNA
/ blood
Cohort Studies
Female
Gene Silencing
Humans
Longitudinal Studies
Lung Neoplasms
/ blood
Male
Middle Aged
Mutation
/ genetics
Platinum
/ therapeutic use
Polymorphism, Single Nucleotide
/ genetics
Prognosis
Smoking
/ adverse effects
Chemotherapy
CtDNA
Efficacy
Lung adenocarcinoma
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
10 10 2019
10 10 2019
Historique:
received:
07
07
2019
accepted:
25
09
2019
entrez:
11
10
2019
pubmed:
11
10
2019
medline:
14
8
2020
Statut:
epublish
Résumé
Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response. We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations. We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy. Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.
Identifiants
pubmed: 31597567
doi: 10.1186/s12967-019-2087-9
pii: 10.1186/s12967-019-2087-9
pmc: PMC6785899
doi:
Substances chimiques
Circulating Tumor DNA
0
Platinum
49DFR088MY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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