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- Title
Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.
- Authors
Debackere, Koen; Marcelis, Lukas; Demeyer, Sofie; Vanden Bempt, Marlies; Mentens, Nicole; Gielen, Olga; Jacobs, Kris; Broux, Michael; Verhoef, Gregor; Michaux, Lucienne; Graux, Carlos; Wlodarska, Iwona; Gaulard, Philippe; de Leval, Laurence; Tousseyn, Thomas; Cools, Jan; Dierickx, Daan
- Abstract
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs. Peripheral T cell lymphoma (PTCL) not otherwise specified (NOS) is a subgroup of PTCL, which has no distinctive features and is poorly characterized at the genetic level. Here, the authors identify two fusion transcripts that activate T cell receptor complex signalling and confer therapeutic vulnerability in PTCL-NOS.
- Subjects
T cell receptors; T-cell lymphoma; CELL communication; RNA sequencing; PROGNOSIS; T cells
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-24037-4