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Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing
- Source :
- Lung, 194(1), 125-135. Springer New York, Maki-Nevala, S, Sarhadi, V K, Knuuttila, A, Scheinin, I, Ellonen, P, Lagstrom, S, Ronty, M, Kettunen, E, Husgafvel-Pursiainen, K, Wolff, H & Knuutila, S 2016, ' Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing ', Lung, vol. 194, no. 1, pp. 125-135 . https://doi.org/10.1007/s00408-015-9814-7
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Abstract
- Background Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM. MethodsExome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM. ResultsIn asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs. ConclusionBAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.
- Subjects :
- Lung adenocarcinoma
Exome sequencing
0301 basic medicine
Male
Mesothelioma
Pathology
Lung Neoplasms
DNA Mutational Analysis
Semaphorins
SUSCEPTIBILITY
Gene mutation
medicine.disease_cause
0302 clinical medicine
CDKN2A
PLEURAL MESOTHELIOMA
Exome
Peptide Synthases
Peritoneal Neoplasms
BAP1
Membrane Glycoproteins
CANCER
3. Good health
ErbB Receptors
030220 oncology & carcinogenesis
SURVIVAL
Female
KRAS
Ubiquitin Thiolesterase
Pulmonary and Respiratory Medicine
Proto-Oncogene Proteins B-raf
Ribosomal Proteins
medicine.medical_specialty
CARCINOMA
EGFR
Pleural Neoplasms
Adenocarcinoma
Coatomer Protein
Polymorphism, Single Nucleotide
Mitochondrial Proteins
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
medicine
Humans
HRAS
GENOME-WIDE ASSOCIATION
EMBEDDED TUMOR MATERIAL
BAP1 MUTATIONS
Receptors, Eph Family
business.industry
Tumor Suppressor Proteins
Mesothelioma, Malignant
Asbestos
medicine.disease
Phosphoric Monoester Hydrolases
030104 developmental biology
3121 General medicine, internal medicine and other clinical medicine
Mutation
Cancer research
business
Cell Adhesion Molecules
Subjects
Details
- Language :
- English
- ISSN :
- 03412040
- Database :
- OpenAIRE
- Journal :
- Lung, 194(1), 125-135. Springer New York, Maki-Nevala, S, Sarhadi, V K, Knuuttila, A, Scheinin, I, Ellonen, P, Lagstrom, S, Ronty, M, Kettunen, E, Husgafvel-Pursiainen, K, Wolff, H & Knuutila, S 2016, ' Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing ', Lung, vol. 194, no. 1, pp. 125-135 . https://doi.org/10.1007/s00408-015-9814-7
- Accession number :
- edsair.doi.dedup.....020e6140e6e7e43843cede8682e39fbd