Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34140493.
- Also identified by DOI 10.1038/s41467-021-24037-4 and PMC identifier 8211700.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- DNA-Binding Proteins
- Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
- Lymphoma, T-Cell, Peripheral
- Oncogene Proteins, Fusion
- Proto-Oncogene Proteins c-fyn
- RNA-Binding Proteins
- Receptors, Antigen, T-Cell