Details

Autor(en) / Beteiligte

• Moffitt, Andrea B
• Ondrejka, Sarah L
• McKinney, Matthew
• Rempel, Rachel E
• Goodlad, John R
• Teh, Chun Huat
• Leppa, Sirpa
• Mannisto, Susanna
• Kovanen, Panu E
• Tse, Eric
• Au-Yeung, Rex K H
• Kwong, Yok-Lam
• Srivastava, Gopesh
• Iqbal, Javeed
• Yu, Jiayu
• Naresh, Kikkeri
• Villa, Diego
• Gascoyne, Randy D
• Said, Jonathan
• Czader, Magdalena B
• Chadburn, Amy
• Richards, Kristy L
• Rajagopalan, Deepthi
• Davis, Nicholas S
• Smith, Eileen C
• Palus, Brooke C
• Tzeng, Tiffany J
• Healy, Jane A
• Lugar, Patricia L
• Datta, Jyotishka
• Love, Cassandra
• Levy, Shawn
• Dunson, David B
• Zhuang, Yuan
• Hsi, Eric D
• Dave, Sandeep S

Titel

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Ist Teil von

• The Journal of experimental medicine, 2017-05, Vol.214 (5), p.1371-1386

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in as well as , , , and We also identified mutations in , , and Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.