The Genetic Basis of Hepatosplenic T Cell Lymphoma.
Publisher DOI
PubMed ID
28122867
Abstract
Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets.
Date Issued
2017-04
Publication Type
Article
Language(s)
en
Author(s)
McKinney, Matthew | |
Moffitt, Andrea B | |
Gaulard, Philippe | |
Travert, Marion | |
De Leval, Laurence | |
Raffeld, Mark | |
Jaffe, Elaine S | |
Pittaluga, Stefania | |
Xi, Liqiang | |
Heavican, Tayla | |
Iqbal, Javeed | |
Belhadj, Karim | |
Delfau-Larue, Marie Helene | |
Fataccioli, Virginie | |
Czader, Magdalena B | |
Lossos, Izidore S | |
Chapman-Fredricks, Jennifer R | |
Richards, Kristy L | |
Fedoriw, Yuri | |
Ondrejka, Sarah L | |
Hsi, Eric D | |
Low, Lawrence | |
Weisenburger, Dennis | |
Chan, Wing C | |
Mehta-Shah, Neha | |
Horwitz, Steven | |
Bernal-Mizrachi, Leon | |
Flowers, Christopher R | |
Beaven, Anne W | |
Parihar, Mayur | |
Baseggio, Lucile | |
Parrens, Marie | |
Moreau, Anne | |
Sujobert, Pierre | |
Pilichowska, Monika | |
Evens, Andrew M | |
Chadburn, Amy | |
Au-Yeung, Rex K H | |
Srivastava, Gopesh | |
Choi, William W L | |
Goodlad, John R | |
Aurer, Igor | |
Basic-Kinda, Sandra | |
Gascoyne, Randy D | |
Davis, Nicholas S | |
Li, Guojie | |
Zhang, Jenny | |
Rajagopalan, Deepthi | |
Reddy, Anupama | |
Love, Cassandra | |
Levy, Shawn | |
Zhuang, Yuan | |
Datta, Jyotishka | |
Dunson, David B | |
Dave, Sandeep S |
Additional Credits
Journal
Cancer discovery
Publisher
American Association for Cancer Research
ISSN
2159-8290
Access(Rights)
Unknown