Whole exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A and CUL1 in malignant pleural mesothelioma.

Guo G1, Chmielecki J1, Goparaju C2, Heguy A3, Dolgalev I3, Carbone M4, Seepo S1, Meyerson M1, Pass HI5.

Author information

1Broad Institute of Harvard and MIT.
2Department of Cardiothoracic Surgery, NYU Langone Medical Center.
3Genome Technology Center, NYU Langone Medical Center.
4University of Hawaii Cancer Center.
5Department of Cardiothoracic Surgery, NYU Langone Medical Center harvey.pass@nyumc.org.

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 (SCNAs) revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM.

TimAllenMDJD

Wednesday, December 10, 2014