Integrative molecular characterization of malignant pleural mesothelioma Journal Article


Authors: Hmeljak, J.; Sanchez-Vega, F.; Hoadley, K. A.; Shih, J.; Stewart, C.; Heiman, D.; Tarpey, P.; Danilova, L.; Drill, E.; Gibb, E. A.; Bowlby, R.; Kanchi, R.; Osmanbeyoglu, H. U.; Sekido, Y.; Takeshita, J.; Newton, Y.; Graim, K.; Gupta, M.; Gay, C. M.; Diao, L.; Gibbs, D. L.; Thorsson, V.; Iype, L.; Kantheti, H.; Severson, D. T.; Ravegnini, G.; Desmeules, P.; Jungbluth, A. A.; Travis, W. D.; Dacic, S.; Chirieac, L. R.; Galateau-Sallé, F.; Fujimoto, J.; Husain, A. N.; Silveira, H. C.; Rusch, V. W.; Rintoul, R. C.; Pass, H.; Kindler, H.; Zauderer, M. G.; Kwiatkowski, D. J.; Bueno, R.; Tsao, A. S.; Creaney, J.; Lichtenberg, T.; Leraas, K.; Bowen, J.; TCGA Research Network; Felau, I.; Zenklusen, J. C.; Akbani, R.; Cherniack, A. D.; Byers, L. A.; Noble, M. S.; Fletcher, J. A.; Robertson, A. G.; Shen, R.; Aburatani, H.; Robinson, B. W.; Campbell, P.; Ladanyi, M.
Article Title: Integrative molecular characterization of malignant pleural mesothelioma
Abstract: Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expresssion of the immune-checkpoint gene VISTA in epithelioid MPM. © 2018 AACR.
Journal Title: Cancer Discovery
Volume: 8
Issue: 12
ISSN: 2159-8274
Publisher: American Association for Cancer Research  
Date Published: 2018-12-01
Start Page: 1549
End Page: 1565
Language: English
DOI: 10.1158/2159-8290.Cd-18-0804
PROVIDER: scopus
PMCID: PMC6310008
PUBMED: 30322867
DOI/URL:
Notes: Export Date: 2 January 2019 -- Article -- Source: Scopus
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MSK Authors
  1. Valerie W Rusch
    651 Rusch
  2. Ronglai Shen
    127 Shen
  3. Marc Ladanyi
    861 Ladanyi
  4. William D Travis
    548 Travis
  5. Achim Jungbluth
    337 Jungbluth
  6. Esther Naomi Drill
    25 Drill