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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864Rusch -
204Shen -
1326Ladanyi -
743Travis -
188Zauderer -
454Jungbluth -
93Drill -
14Osmanbeyoglu -
8Hmeljak -
137Sanchez Vega
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