Tracking longitudinal genetic changes of circulating tumor DNA (ctDNA) in advanced Lung adenocarcinoma treated with chemotherapy.
J Transl Med
; 17(1): 339, 2019 10 10.
Article
en En
| MEDLINE
| ID: mdl-31597567
ABSTRACT
INTRODUCTION:
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. MATERIALS ANDMETHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN Tumoral Circulante
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Adenocarcinoma del Pulmón
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Neoplasias Pulmonares
Tipo de estudio:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Transl Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
China