The Genetic Basis of Hepatosplenic T Cell Lymphoma.

McKinney, Matthew; Moffitt, Andrea B; Gaulard, Philippe; Travert, Marion; De Leval, Laurence; Nicolae, Alina; 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; ... (2017). The Genetic Basis of Hepatosplenic T Cell Lymphoma. Cancer discovery, 7(4), pp. 369-379. American Association for Cancer Research 10.1158/2159-8290.CD-16-0330

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Nicolae, Alina

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2159-8290

Publisher:

American Association for Cancer Research

Language:

English

Submitter:

Ekkehard Hewer

Date Deposited:

11 Jul 2017 13:01

Last Modified:

11 Jul 2017 13:01

Publisher DOI:

10.1158/2159-8290.CD-16-0330

PubMed ID:

28122867

URI:

https://boris.unibe.ch/id/eprint/95936

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