Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma
Creators: name: Jones, Christine L.
name: Degasperi, Andrea
name: Grandi, Vieri
name: Amarante, Tauanne D.
name: Mitchell, Tracey J.
name: Nik-Zainal, Serena
name: Whittaker, Sean J.
name: Ambrose, John C.
name: Arumugam, Prabhu
name: Baple, Emma L.
name: Bleda, Marta
name: Boardman-Pretty, Freya
name: Boissiere, Jeanne M.
name: Boustred, Christopher R.
name: Brittain, Helen
name: Caulfield, Mark J.
name: Chan, Georgia C.
name: Craig, Clare E. H.
name: Daugherty, Louise C.
name: De Burca, Anna
name: Devereau, Andrew
name: Elgar, Greg
name: Foulger, Rebecca E.
name: Fowler, Tom
name: Furió-Tarí, Pedro
name: Giess, Adam
name: Hackett, Joanne M.
name: Halai, Dina
name: Hamblin, Angela
name: Henderson, Shirley
name: Holman, James E.
name: Hubbard, Tim J. P.
name: Ibáñez, Kristina
name: Jackson, Rob
name: Jones, Louise J.
name: Kasperaviciute, Dalia
name: Kayikci, Melis
name: Kousathanas, Athanasios
name: Lahnstein, Lea
name: Lawson, Kay
name: Leigh, Sarah E. A.
name: Leong, Ivonne U. S.
name: Lopez, Javier F.
name: Maleady-Crowe, Fiona
name: Mason, Joanne
name: McDonagh, Ellen M.
name: Moutsianas, Loukas
name: Mueller, Michael
name: Murugaesu, Nirupa
name: Need, Anna C.
name: O’Donovan, Peter
name: Odhams, Chris A.
name: Orioli, Andrea
name: Patch, Christine
name: Pereira, Mariana Buongermino
name: Perez-Gil, Daniel
name: Polychronopoulos, Dimitris
name: Pullinger, John
name: Rahim, Tahrima
name: Rendon, Augusto
name: Riesgo-Ferreiro, Pablo
name: Rogers, Tim
name: Ryten, Mina
name: Savage, Kevin
name: Sawant, Kushmita
name: Scott, Richard H.
name: Siddiq, Afshan
name: Sieghart, Alexander
name: Smedley, Damian
name: Smith, Katherine R.
name: Smith, Samuel C.
name: Sosinsky, Alona
name: Spooner, William
name: Stevens, Helen E.
name: Stuckey, Alexander
name: Sultana, Razvan
name: Tanguy, Mélanie
name: Thomas, Ellen R. A.
name: Thompson, Simon R.
name: Tregidgo, Carolyn
name: Tucci, Arianna
name: Walsh, Emma
name: Watters, Sarah A.
name: Welland, Matthew J.
name: Williams, Eleanor
name: Witkowska, Katarzyna
name: Wood, Suzanne M.
name: Zarowiecki, Magdalena
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Article
/631/67/1990/291/1621/1916
/631/67/69
article

description: Funder: Galderma; doi: http://dx.doi.org/10.13039/501100009754
description: Funder: NIHR-BRC Cambridge core grant
description: Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272
description: Funder: NHS England
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.