Authors
Raphael Bueno, Eric W Stawiski, Leonard D Goldstein, Steffen Durinck, Assunta De Rienzo, Zora Modrusan, Florian Gnad, Thong T Nguyen, Bijay S Jaiswal, Lucian R Chirieac, Daniele Sciaranghella, Nhien Dao, Corinne E Gustafson, Kiara J Munir, Jason A Hackney, Amitabha Chaudhuri, Ravi Gupta, Joseph Guillory, Karen Toy, Connie Ha, Ying-Jiun Chen, Jeremy Stinson, Subhra Chaudhuri, Na Zhang, Thomas D Wu, David J Sugarbaker, Frederic J de Sauvage, William G Richards, Somasekar Seshagiri
Publication date
2016/4
Journal
Nature genetics
Volume
48
Issue
4
Pages
407-416
Publisher
Nature Publishing Group US
Description
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 …
Scholar articles
R Bueno, EW Stawiski, LD Goldstein, S Durinck… - Nature genetics, 2016