期刊
SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41598-021-83352-4
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资金
- Galderma
- CRUK Pioneer Award [C60100/A23433]
- CRUK Advanced Clinician Scientist Fellowship [C60100/A23916]
- NIHR-BRC Cambridge core grant
- Wellcome-Beit Prize
- Wellcome Trust Strategic Award [WT100126/B/13/Z]
- CRUK PRECISION Grand Challenge award
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust
- NIHR Clinical Research Facility
- National Institute for Health Research
- NHS England
- Wellcome Trust
- Cancer Research UK
- Medical Research Council
- King's College London
- MRC [MC_PC_14089, MC_EX_MR/M009203/1, MR/M009203/1] Funding Source: UKRI
This study identified different mutational signatures and associated recurrent gene mutations in various subtypes of T-cell non-Hodgkin's lymphomas. UV radiation was found to have a strong correlation with cutaneous T-cell lymphoma. This finding highlights the importance of understanding the pathogenesis of the disease.
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.
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