Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing

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http://hdl.handle.net/10138/297141

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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

Title: Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing
Author: Maki-Nevala, Satu; Sarhadi, Virinder Kaur; Knuuttila, Aija; Scheinin, Ilari; Ellonen, Pekka; Lagstrom, Sonja; Ronty, Mikko; Kettunen, Eeva; Husgafvel-Pursiainen, Kirsti; Wolff, Henrik; Knuutila, Sakari
Contributor organization: Department of Pathology
Medicum
Clinicum
Department of Medicine
Keuhkosairauksien yksikkö
Sakari Knuutila / Principal Investigator
Institute for Molecular Medicine Finland
Date: 2016-02
Language: eng
Number of pages: 11
Belongs to series: Lung
ISSN: 0341-2040
DOI: https://doi.org/10.1007/s00408-015-9814-7
URI: http://hdl.handle.net/10138/297141
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.
Subject: Asbestos
Mutation
Lung adenocarcinoma
Mesothelioma
Exome sequencing
GENOME-WIDE ASSOCIATION
EMBEDDED TUMOR MATERIAL
PLEURAL MESOTHELIOMA
BAP1 MUTATIONS
CANCER
CARCINOMA
EGFR
KRAS
SUSCEPTIBILITY
SURVIVAL
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess


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