Oncotarget

Research Papers:

Targeted next generation sequencing identified a high frequency genetic mutated profile in wood smoke exposure-related lung adenocarcinoma patients

Giovanny Soca-Chafre, Norma Hernández-Pedro, Alejandro Aviles-Salas, Carmen Alaez Versón, Karol Carrillo Sánchez, Andrés F. Cardona, Federico Avila-Moreno, Pedro Barrios-Bernal, Diana Flores-Estrada and Oscar Arrieta _

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Oncotarget. 2018; 9:30499-30512. https://doi.org/10.18632/oncotarget.25369

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Abstract

Giovanny Soca-Chafre1, Norma Hernández-Pedro1, Alejandro Aviles-Salas2, Carmen Alaez Versón3, Karol Carrillo Sánchez3, Andrés F. Cardona4, Federico Avila-Moreno5,6, Pedro Barrios-Bernal1, Diana Flores-Estrada7 and Oscar Arrieta1,7

1Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN) México City, México

2Department of Pathology, INCAN, México City, México

3Translational Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), México City, México

4Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia

5Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores (FES) Iztacala, Biomedicine Research Unit, Cancer Epigenomics and Lung Diseases Laboratory 12, México State, México

6National Institute of Respiratory Diseases (INER) “Ismael Cosío Villegas”, Research Unit, México City, México

7Thoracic Oncology Clinic, INCAN, México City, México

Correspondence to:

Oscar Arrieta, email: ogarrieta@unam.mx

Keywords: lung adenocarcinoma; wood smoke exposure; genotyping; mutation profile

Received: January 30, 2018    Accepted: April 21, 2018    Published: July 17, 2018

ABSTRACT

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.


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