Targeted next generation sequencing identified a high frequency genetic mutated profile in wood smoke exposure-related lung adenocarcinoma patients
Por:
Soca-Chafre G., Hernández-Pedro N., Aviles-Salas A., Versón C.A., Sánchez K.C., Cardona A.F., Avila-Moreno F., Barrios-Bernal P., Flores-Estrada D., Arrieta O.
Publicada:
1 ene 2018
Categoría:
Oncology
Resumen:
Background: Wood smoke exposure (WSE) has been associated with an increased risk of lung cancer development. WSE has been related with high frequency of EGFR mutations and low frequency of KRAS mutations. The aim of this study was to evaluate large scale genomic alterations in lung adenocarcinomas associated with WSE using targeted next generation sequencing. Methods: DNA multi-targeted sequencing was performed in 42 fresh-frozen samples of advanced lung adenocarcinomas. The TruSeQ Cancer Panel (Illumina) was used for genomic library construction and sequencing assays. Results: WSE rate was higher in women (p=0.037) and non-smokers (p=0.001). WSE correlated with mutations in the genes SMARCB1 (p=0.002), Ataxia telangiectasia mutated (p=0.004), Kinase Insert Domain Receptor (p=0.006), and were borderline significant in RET and EGFR exon. Genomic alterations significantly co-occurred in the tumor suppressor gene ATM with the following genes: SMARCB1, EGFR exon 7, RET and KDR. Clinical factors associated with poor prognosis were ECOG = 2 (p= 0.014), mutations in KDR (p= 0.004) and APC genes (p < 0.001). Conclusions: Lung adenocarcinoma patients with WSE showed a distinctive mutated profile for the SMARCB1, ATM, EGFR exon 7, RET and KDR genes. ECOG status and KDR gene mutations were significantly associated with poor prognosis. © Soca-Chafre et al.
Filiaciones:
Soca-Chafre G.:
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN) México City, México, Mexico
Hernández-Pedro N.:
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN) México City, México, Mexico
Aviles-Salas A.:
Department of Pathology, INCAN, Mexico City, Mexico
Versón C.A.:
Translational Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
Sánchez K.C.:
Translational Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
Cardona A.F.:
Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia
Avila-Moreno F.:
Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores (FES) Iztacala, Biomedicine Research Unit, Cancer Epigenomics and Lung Diseases Laboratory 12, México State, Mexico
National Institute of Respiratory Diseases (INER), 'Ismael Cosío Villegas', Research Unit, México City, Mexico
Barrios-Bernal P.:
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN) México City, México, Mexico
Flores-Estrada D.:
Thoracic Oncology Clinic, INCan, Mexico City, Mexico
Arrieta O.:
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN) México City, México, Mexico
Thoracic Oncology Clinic, INCan, Mexico City, Mexico
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