title: Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts. Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Guo
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts. Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.affiliation: Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York, New York.
authors.forename: Chandra
authors.initials: C
authors.lastname: Goparaju
authors.affiliation: Genome Technology Center, NYU Langone Medical Center, New York, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Heguy
authors.affiliation: Genome Technology Center, NYU Langone Medical Center, New York, New York.
authors.forename: Igor
authors.initials: I
authors.lastname: Dolgalev
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Sara
authors.initials: S
authors.lastname: Seepo
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts. Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Pathology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York, New York. Harvey.Pass@nyumc.org.
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
mesh_terms: D044842:Cullin Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D059472:Exome; D018628:Gene Dosage; D006801:Humans; D008654:Mesothelioma / Q000235:genetics*; D009154:Mutation; D025581:Neurofibromin 2 / Q000235:genetics*; D010997:Pleural Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; C100318:Cullin 1; D044842:Cullin Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D025581:Neurofibromin 2; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase