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Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified
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,...
| Autores principales: | , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211700/ https://www.ncbi.nlm.nih.gov/pubmed/34140493 http://dx.doi.org/10.1038/s41467-021-24037-4 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Debackere, Koen |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8211700 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-82117002021-07-01 Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified 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 Nat Commun Article 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. Nature Publishing Group UK 2021-06-17 /pmc/articles/PMC8211700/ /pubmed/34140493 http://dx.doi.org/10.1038/s41467-021-24037-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article 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 Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified |
| title | Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified |
| title_full | Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified |
| title_fullStr | Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified |
| title_full_unstemmed | Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified |
| title_short | Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified |
| title_sort | fusion transcripts fyn-traf3ip2 and khdrbs1-lck hijack t cell receptor signaling in peripheral t-cell lymphoma, not otherwise specified |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211700/ https://www.ncbi.nlm.nih.gov/pubmed/34140493 http://dx.doi.org/10.1038/s41467-021-24037-4 |
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