Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Debackere, K.; Marcelis, L.; Demeyer, S.; Vanden Bempt, M.; Mentens, N.; Gielen, O.; Jacobs, K.; Broux, M.; Verhoef, G.; Michaux, L.; Graux, C.; Wlodarska, I.; Gaulard, P.; de Leval, L.; Tousseyn, T.; Cools, J.; Dierickx, D.

doi:10.1038/s41467-021-24037-4

Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Détails

Télécharger: 41467_2021_Article_24037.pdf (5786.11 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0

ID Serval

serval:BIB_F9F211DA3132

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Périodique

Nature communications

Auteur⸱e⸱s

Debackere K., Marcelis L., Demeyer S., Vanden Bempt M., Mentens N., Gielen O., Jacobs K., Broux M., Verhoef G., Michaux L., Graux C., Wlodarska I., Gaulard P., de Leval L., Tousseyn T., Cools J., Dierickx D.

ISSN

2041-1723 (Electronic)

ISSN-L

2041-1723

Statut éditorial

Publié

Date de publication

17/06/2021

Peer-reviewed

Oui

Volume

Numéro

Pages

3705

Langue

anglais

Notes

Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish

Résumé

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.

Mots-clé

Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Animals, Cell Line, Tumor, Cell Membrane/metabolism, Cohort Studies, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Forkhead Box Protein O1/genetics, Forkhead Box Protein O1/metabolism, Gene Expression Regulation, Neoplastic/genetics, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Kaplan-Meier Estimate, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism, Lymphoma, T-Cell, Peripheral/genetics, Lymphoma, T-Cell, Peripheral/metabolism, Lymphoma, T-Cell, Peripheral/pathology, Mice, Mice, Inbred C57BL, NF-kappa B/metabolism, Oncogene Proteins, Fusion/genetics, Oncogene Proteins, Fusion/metabolism, Proto-Oncogene Proteins c-fyn/genetics, Proto-Oncogene Proteins c-fyn/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, RNA-Seq, Receptors, Antigen, T-Cell/metabolism, Signal Transduction/genetics, Sin3 Histone Deacetylase and Corepressor Complex/genetics, Sin3 Histone Deacetylase and Corepressor Complex/metabolism, bcl-X Protein/antagonists & inhibitors, bcl-X Protein/metabolism

URN

urn:nbn:ch:serval-BIB_F9F211DA31327

OAI-PMH

oai:serval.unil.ch:BIB_F9F211DA3132

DOI

10.1038/s41467-021-24037-4

Pubmed

34140493

Web of science

000665032700027

Open Access

Oui