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Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations.
Bueno, Raphael; Stawiski, Eric W; Goldstein, Leonard D; Durinck, Steffen; De Rienzo, Assunta; Modrusan, Zora; Gnad, Florian; Nguyen, Thong T; Jaiswal, Bijay S; Chirieac, Lucian R; Sciaranghella, Daniele; Dao, Nhien; Gustafson, Corinne E; Munir, Kiara J; Hackney, Jason A; Chaudhuri, Amitabha; Gupta, Ravi; Guillory, Joseph; Toy, Karen; Ha, Connie; Chen, Ying-Jiun; Stinson, Jeremy; Chaudhuri, Subhra; Zhang, Na; Wu, Thomas D; Sugarbaker, David J; de Sauvage, Frederic J; Richards, William G; Seshagiri, Somasekar.
Affiliation
  • Bueno R; Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Stawiski EW; Bioinformatics and Computational Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Goldstein LD; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Durinck S; Bioinformatics and Computational Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • De Rienzo A; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Modrusan Z; Bioinformatics and Computational Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Gnad F; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Nguyen TT; Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Jaiswal BS; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Chirieac LR; Bioinformatics and Computational Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Sciaranghella D; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Dao N; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Gustafson CE; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Munir KJ; Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Hackney JA; Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Chaudhuri A; Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Gupta R; Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Guillory J; Bioinformatics and Computational Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Toy K; Bioinformatics Department, MedGenome Labs, Pvt., Ltd., Narayana Health City, Bangalore, India.
  • Ha C; Bioinformatics Department, MedGenome Labs, Pvt., Ltd., Narayana Health City, Bangalore, India.
  • Chen YJ; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Stinson J; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Chaudhuri S; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Zhang N; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Wu TD; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Sugarbaker DJ; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • de Sauvage FJ; Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Richards WG; Bioinformatics and Computational Biology Department, Genentech, Inc., South San Francisco, California, USA.
  • Seshagiri S; Division of Thoracic Surgery, Baylor College of Medicine, Houston, Texas, USA.
Nat Genet ; 48(4): 407-16, 2016 Apr.
Article de En | MEDLINE | ID: mdl-26928227
ABSTRACT
We analyzed transcriptomes (n = 211), whole exomes (n = 99) and targeted exomes (n = 103) from 216 malignant pleural mesothelioma (MPM) tumors. Using RNA-seq data, we identified four distinct molecular subtypes sarcomatoid, epithelioid, biphasic-epithelioid (biphasic-E) and biphasic-sarcomatoid (biphasic-S). Through exome analysis, we found BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1 and DDX51 to be significantly mutated (q-score ≥ 0.8) in MPMs. We identified recurrent mutations in several genes, including SF3B1 (∼2%; 4/216) and TRAF7 (∼2%; 5/216). SF3B1-mutant samples showed a splicing profile distinct from that of wild-type tumors. TRAF7 alterations occurred primarily in the WD40 domain and were, except in one case, mutually exclusive with NF2 alterations. We found recurrent gene fusions and splice alterations to be frequent mechanisms for inactivation of NF2, BAP1 and SETD2. Through integrated analyses, we identified alterations in Hippo, mTOR, histone methylation, RNA helicase and p53 signaling pathways in MPMs.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs de la plèvre / Protéines de fusion oncogènes / Tumeurs du poumon / Mésothéliome Type d'étude: Prognostic_studies / Systematic_reviews Limites: Humans Langue: En Journal: Nat Genet Sujet du journal: GENETICA MEDICA Année: 2016 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs de la plèvre / Protéines de fusion oncogènes / Tumeurs du poumon / Mésothéliome Type d'étude: Prognostic_studies / Systematic_reviews Limites: Humans Langue: En Journal: Nat Genet Sujet du journal: GENETICA MEDICA Année: 2016 Type de document: Article Pays d'affiliation: États-Unis d'Amérique