Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
| Autor: | Jones, Christine L., Degasperi, Andrea, Grandi, Vieri, Amarante, Tauanne D., Mitchell, Tracey J., Nik-Zainal, Serena, Whittaker, Sean J., Ambrose, John C., Arumugam, Prabhu, Baple, Emma L., Bleda, Marta, Boardman-Pretty, Freya, Boissiere, Jeanne M., Boustred, Christopher R., Brittain, Helen, Caulfield, Mark J., Chan, Georgia C., Craig, Clare E. H., Daugherty, Louise C., De Burca, Anna, Devereau, Andrew, Elgar, Greg, Foulger, Rebecca E., Fowler, Tom, Furió-Tarí, Pedro, Giess, Adam, Hackett, Joanne M., Halai, Dina, Hamblin, Angela, Henderson, Shirley, Holman, James E., Hubbard, Tim J. P., Ibáñez, Kristina, Jackson, Rob, Jones, Louise J., Kasperaviciute, Dalia, Kayikci, Melis, Kousathanas, Athanasios, Lahnstein, Lea, Lawson, Kay, Leigh, Sarah E. A., Leong, Ivonne U. S., Lopez, Javier F., Maleady-Crowe, Fiona, Mason, Joanne, McDonagh, Ellen M., Moutsianas, Loukas, Mueller, Michael, Murugaesu, Nirupa, Need, Anna C., O’Donovan, Peter, Odhams, Chris A., Orioli, Andrea, Patch, Christine, Pereira, Mariana Buongermino, Perez-Gil, Daniel, Polychronopoulos, Dimitris, Pullinger, John, Rahim, Tahrima, Rendon, Augusto, Riesgo-Ferreiro, Pablo, Rogers, Tim, Ryten, Mina, Savage, Kevin, Sawant, Kushmita, Scott, Richard H., Siddiq, Afshan, Sieghart, Alexander, Smedley, Damian, Smith, Katherine R., Smith, Samuel C., Sosinsky, Alona, Spooner, William, Stevens, Helen E., Stuckey, Alexander, Sultana, Razvan, Tanguy, Mélanie, Thomas, Ellen R. A., Thompson, Simon R., Tregidgo, Carolyn, Tucci, Arianna, Walsh, Emma, Watters, Sarah A., Welland, Matthew J., Williams, Eleanor, Witkowska, Katarzyna, Wood, Suzanne M., Zarowiecki, Magdalena |
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| Přispěvatelé: | Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: | |
| Popis: | Funder: Galderma; doi: http://dx.doi.org/10.13039/501100009754 Funder: NIHR-BRC Cambridge core grant Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272 Funder: NHS England 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. |
| Databáze: | OpenAIRE |
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