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Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non Hodgkin lymphomas(1,2). Here we combined whole exome sequencing of 12 tumor-normal DNA pairs, RNAseq analysis and targeted deep sequencing to identify new genetic alterations in PTCL transformation. These anal...

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Autores principales: Palomero, Teresa, Couronné, Lucile, Khiabanian, Hossein, Kim, Mi-Yeon, Ambesi-Impiombato, Alberto, Perez-Garcia, Arianne, Carpenter, Zachary, Abate, Francesco, Allegretta, Maddalena, Haydu, J. Erika, Jiang, Xiaoyu, Lossos, Izidore S., Nicolas, Concha, Balbin, Milagros, Bastard, Christian, Bhagat, Govind, Piris, Miguel Angel, Campo, Elias, Bernard, Olivier, Rabadan, Raul, Ferrando, Adolfo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963408/
https://www.ncbi.nlm.nih.gov/pubmed/24413734
http://dx.doi.org/10.1038/ng.2873
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author Palomero, Teresa
Couronné, Lucile
Khiabanian, Hossein
Kim, Mi-Yeon
Ambesi-Impiombato, Alberto
Perez-Garcia, Arianne
Carpenter, Zachary
Abate, Francesco
Allegretta, Maddalena
Haydu, J. Erika
Jiang, Xiaoyu
Lossos, Izidore S.
Nicolas, Concha
Balbin, Milagros
Bastard, Christian
Bhagat, Govind
Piris, Miguel Angel
Campo, Elias
Bernard, Olivier
Rabadan, Raul
Ferrando, Adolfo
author_facet Palomero, Teresa
Couronné, Lucile
Khiabanian, Hossein
Kim, Mi-Yeon
Ambesi-Impiombato, Alberto
Perez-Garcia, Arianne
Carpenter, Zachary
Abate, Francesco
Allegretta, Maddalena
Haydu, J. Erika
Jiang, Xiaoyu
Lossos, Izidore S.
Nicolas, Concha
Balbin, Milagros
Bastard, Christian
Bhagat, Govind
Piris, Miguel Angel
Campo, Elias
Bernard, Olivier
Rabadan, Raul
Ferrando, Adolfo
author_sort Palomero, Teresa
collection PubMed
description Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non Hodgkin lymphomas(1,2). Here we combined whole exome sequencing of 12 tumor-normal DNA pairs, RNAseq analysis and targeted deep sequencing to identify new genetic alterations in PTCL transformation. These analyses identified highly recurrent epigenetic factor mutations in TET2, DNMT3A and IDH2 as well as a new highly prevalent RHOA p.Gly17Val (NM_001664) mutation present in 22/35 (67%) of angioimmunoblastic T-cell lymphomas (AITL) and in 8/44 (18%) not otherwise specified PTCL (PTCL NOS) samples. Mechanistically, the RHOA Gly17Val protein interferes with RHOA signaling in biochemical and cellular assays, an effect potentially mediated by the sequestration of activated Guanine Exchange Factor (GEF) proteins. In addition, we describe new and recurrent, albeit less frequent, genetic defects including mutations in FYN, ATM, B2M and CD58 implicating SRC signaling, impaired DNA damage response and escape from immune surveillance mechanisms in the pathogenesis of PTCL.
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spelling pubmed-39634082014-08-01 Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas Palomero, Teresa Couronné, Lucile Khiabanian, Hossein Kim, Mi-Yeon Ambesi-Impiombato, Alberto Perez-Garcia, Arianne Carpenter, Zachary Abate, Francesco Allegretta, Maddalena Haydu, J. Erika Jiang, Xiaoyu Lossos, Izidore S. Nicolas, Concha Balbin, Milagros Bastard, Christian Bhagat, Govind Piris, Miguel Angel Campo, Elias Bernard, Olivier Rabadan, Raul Ferrando, Adolfo Nat Genet Article Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non Hodgkin lymphomas(1,2). Here we combined whole exome sequencing of 12 tumor-normal DNA pairs, RNAseq analysis and targeted deep sequencing to identify new genetic alterations in PTCL transformation. These analyses identified highly recurrent epigenetic factor mutations in TET2, DNMT3A and IDH2 as well as a new highly prevalent RHOA p.Gly17Val (NM_001664) mutation present in 22/35 (67%) of angioimmunoblastic T-cell lymphomas (AITL) and in 8/44 (18%) not otherwise specified PTCL (PTCL NOS) samples. Mechanistically, the RHOA Gly17Val protein interferes with RHOA signaling in biochemical and cellular assays, an effect potentially mediated by the sequestration of activated Guanine Exchange Factor (GEF) proteins. In addition, we describe new and recurrent, albeit less frequent, genetic defects including mutations in FYN, ATM, B2M and CD58 implicating SRC signaling, impaired DNA damage response and escape from immune surveillance mechanisms in the pathogenesis of PTCL. 2014-01-12 2014-02 /pmc/articles/PMC3963408/ /pubmed/24413734 http://dx.doi.org/10.1038/ng.2873 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Palomero, Teresa
Couronné, Lucile
Khiabanian, Hossein
Kim, Mi-Yeon
Ambesi-Impiombato, Alberto
Perez-Garcia, Arianne
Carpenter, Zachary
Abate, Francesco
Allegretta, Maddalena
Haydu, J. Erika
Jiang, Xiaoyu
Lossos, Izidore S.
Nicolas, Concha
Balbin, Milagros
Bastard, Christian
Bhagat, Govind
Piris, Miguel Angel
Campo, Elias
Bernard, Olivier
Rabadan, Raul
Ferrando, Adolfo
Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
title Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
title_full Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
title_fullStr Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
title_full_unstemmed Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
title_short Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
title_sort recurrent mutations in epigenetic regulators, rhoa and fyn kinase in peripheral t cell lymphomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963408/
https://www.ncbi.nlm.nih.gov/pubmed/24413734
http://dx.doi.org/10.1038/ng.2873
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