Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma

Abstract T-cell non-Hodgkin’s lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin’s lymphoma to identify mutational signatures and associated recurrent gene muta...

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Autores principales:	Christine L. Jones, Andrea Degasperi, Vieri Grandi, Tauanne D. Amarante, Genomics England Research Consortium, Tracey J. Mitchell, Serena Nik-Zainal, Sean J. Whittaker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/14f26d51c7e44279991de8475f3bb7bb
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spelling	oai:doaj.org-article:14f26d51c7e44279991de8475f3bb7bb2021-12-02T14:21:57ZSpectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma10.1038/s41598-021-83352-42045-2322https://doaj.org/article/14f26d51c7e44279991de8475f3bb7bb2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83352-4https://doaj.org/toc/2045-2322Abstract T-cell non-Hodgkin’s lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin’s lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells. Adult T-cell leukemia-lymphoma was specifically associated with signature 17, which was found to correlate with the IRF4 K59R mutation that is exclusive to Adult T-cell leukemia-lymphoma. Signature 7, implicating UV exposure was uniquely identified in cutaneous T-cell lymphoma (CTCL), contributing 52% of the mutational burden in mycosis fungoides and 23% in Sezary syndrome. Importantly this UV signature was observed in CD4 + T-cells isolated from the blood of Sezary syndrome patients suggesting extensive re-circulation of these T-cells through skin and blood. Analysis of non-Hodgkin’s T-cell lymphoma cases submitted to the national 100,000 WGS project confirmed that signature 7 was only identified in CTCL strongly implicating UV radiation in the pathogenesis of cutaneous T-cell lymphoma.Christine L. JonesAndrea DegasperiVieri GrandiTauanne D. AmaranteGenomics England Research ConsortiumTracey J. MitchellSerena Nik-ZainalSean J. WhittakerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christine L. Jones Andrea Degasperi Vieri Grandi Tauanne D. Amarante Genomics England Research Consortium Tracey J. Mitchell Serena Nik-Zainal Sean J. Whittaker Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
description	Abstract T-cell non-Hodgkin’s lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin’s lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells. Adult T-cell leukemia-lymphoma was specifically associated with signature 17, which was found to correlate with the IRF4 K59R mutation that is exclusive to Adult T-cell leukemia-lymphoma. Signature 7, implicating UV exposure was uniquely identified in cutaneous T-cell lymphoma (CTCL), contributing 52% of the mutational burden in mycosis fungoides and 23% in Sezary syndrome. Importantly this UV signature was observed in CD4 + T-cells isolated from the blood of Sezary syndrome patients suggesting extensive re-circulation of these T-cells through skin and blood. Analysis of non-Hodgkin’s T-cell lymphoma cases submitted to the national 100,000 WGS project confirmed that signature 7 was only identified in CTCL strongly implicating UV radiation in the pathogenesis of cutaneous T-cell lymphoma.
format	article
author	Christine L. Jones Andrea Degasperi Vieri Grandi Tauanne D. Amarante Genomics England Research Consortium Tracey J. Mitchell Serena Nik-Zainal Sean J. Whittaker
author_facet	Christine L. Jones Andrea Degasperi Vieri Grandi Tauanne D. Amarante Genomics England Research Consortium Tracey J. Mitchell Serena Nik-Zainal Sean J. Whittaker
author_sort	Christine L. Jones
title	Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
title_short	Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
title_full	Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
title_fullStr	Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
title_full_unstemmed	Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
title_sort	spectrum of mutational signatures in t-cell lymphoma reveals a key role for uv radiation in cutaneous t-cell lymphoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/14f26d51c7e44279991de8475f3bb7bb
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Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma

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