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

Teresa Palomero, Lucile Couronné, Hossein Khiabanian, Mi Yeon Kim, Alberto Ambesi-Impiombato, Arianne Perez-Garcia, Zachary Carpenter, Francesco Abate, Maddalena Allegretta, J. Erika Haydu, Xiaoyu Jiang, Izidore Lossos, Concha Nicolas, Milagros Balbin, Christian Bastard, Govind Bhagat, Miguel A. Piris, Elias Campo, Olivier A. Bernard, Raul Rabadan & 1 others Adolfo A. Ferrando

Research output: Contribution to journalArticle

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Abstract

Peripheral T cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non-Hodgkin lymphomas. Here we combined whole-exome sequencing of 12 tumor-normal DNA pairs, RNA sequencing 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 mutation encoding a p.Gly17Val alteration present in 22 of 35 (67%) angioimmunoblastic T cell lymphoma (AITL) samples and in 8 of 44 (18%) PTCL, not otherwise specified (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.

Original languageEnglish
Pages (from-to)166-170
Number of pages5
JournalNature Genetics
Volume46
Issue number2
DOIs
StatePublished - Jan 1 2014

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Peripheral T-Cell Lymphoma
Epigenomics
Phosphotransferases
Mutation
Exome
RNA Sequence Analysis
High-Throughput Nucleotide Sequencing
T-Cell Lymphoma
Guanine
Non-Hodgkin's Lymphoma
DNA Damage
Proteins
DNA
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Palomero, T., Couronné, L., Khiabanian, H., Kim, M. Y., Ambesi-Impiombato, A., Perez-Garcia, A., ... Ferrando, A. A. (2014). Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nature Genetics, 46(2), 166-170. https://doi.org/10.1038/ng.2873

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; Nicolas, Concha; Balbin, Milagros; Bastard, Christian; Bhagat, Govind; Piris, Miguel A.; Campo, Elias; Bernard, Olivier A.; Rabadan, Raul; Ferrando, Adolfo A.

In: Nature Genetics, Vol. 46, No. 2, 01.01.2014, p. 166-170.

Research output: Contribution to journalArticle

Palomero, T, Couronné, L, Khiabanian, H, Kim, MY, Ambesi-Impiombato, A, Perez-Garcia, A, Carpenter, Z, Abate, F, Allegretta, M, Haydu, JE, Jiang, X, Lossos, I, Nicolas, C, Balbin, M, Bastard, C, Bhagat, G, Piris, MA, Campo, E, Bernard, OA, Rabadan, R & Ferrando, AA 2014, 'Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas', Nature Genetics, vol. 46, no. 2, pp. 166-170. https://doi.org/10.1038/ng.2873
Palomero T, Couronné L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nature Genetics. 2014 Jan 1;46(2):166-170. https://doi.org/10.1038/ng.2873
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 ; Nicolas, Concha ; Balbin, Milagros ; Bastard, Christian ; Bhagat, Govind ; Piris, Miguel A. ; Campo, Elias ; Bernard, Olivier A. ; Rabadan, Raul ; Ferrando, Adolfo A. / Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. In: Nature Genetics. 2014 ; Vol. 46, No. 2. pp. 166-170.
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