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

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Date

17 juin 2021

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Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-24037-4

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/34140493

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/2041-1723

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_F9F211DA31327

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/

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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

Sujets proches En

Proteids Lymphoma Non-Hodgkin's lymphoma Germinoblastomas Sarcoma, Germinoblastic Sarcoma, Immunoblastic Reticulolymphosarcomas Immunoblastomas

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K. Debackere et al., « Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified. », Serveur académique Lausannois, ID : 10.1038/s41467-021-24037-4

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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.

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