EGAGenomicsTranscriptome Analysishttps://ega-archive.org/studies/EGAS00001007606EGAEGA study EGAS00001007606scRNAseq of patients with chronic graft-versus-host-diseaseEGArestrictedMutations, Leu2, Cell., CD8, MAL, p32Allele Frequencies, other disease, d230, Thymus-Dependent Lymphocytes, T-cell surface antigen T4/Leu-3, supply, Neoplasms, Benign Neoplasm, Gene, dTAFII250, T-Lymphocyte, Tumor, Malignant, EfW1, Mutations, dmTAF[[II]]230, Responder protein Smok-Tcr, L3T4, Allele Frequency, diseases, T Lymphocyte, dmTAF1, Taf230, Equilibrium, Ly-4, symptoms, disease or disorder, diseases and disorders, MAL, immature T cell, TAF250, Taf200, human disease, dTAF[[II]]250, Genetic, TFIID TAF250, Malignancy, cel, occurrence, cell, distribution, T-Cells, prevalence, T, Taf1p, non-neoplastic, Neoplasias, dTAF250, T Cells, malignant neoplasm, Clients, mature T cell, disorder, Allele, Homo sapiens disease, Malignancies, TAF, Frequency, T Lymphocytes, Thymus Dependent Lymphocytes, Genetic Equilibrium, Lymphocyte, incidence, Cancer, Tumors, screening, dTAF[[II]]230, TAF[[II]]250, findings, Malignant Neoplasm, T-cell surface antigen T4|Leu-3, T-lymphocyte receptor complex, RnBP, frequency, disorders, TAF200, Leu2, GlcNAc 2-epimerase, l(3)84Ab, medical condition, BG:DS00004.13, TAFII-250, TAF250/230, Client, Cell, dTAF230, TAFII250, 2.7.11.1, N-acetyl-D-glucosamine 2-epimerase, MT, Benign, TCR complex, T-cell differentiation antigen L3T4, T-Cell, Frequencies, p230, RENBP, Diseases, Neoplasm, TAF[[II]]250/230, condition, TFIID, supply and distribution, T lymphocyte, outbreaks, T lymphocyte receptor complex, Taf[[II]]250, TCR, Tcr, Thymus-Dependent Lymphocyte., T-cell, primary cancer, Gene Frequencies, TAF[[II]]230, T-cell surface glycoprotein CD4, p32, Thymus-Dependent, signs, Benign Neoplasms, CD4mut, Lymphocytes, TAF[II]250, Cancers, T-lymphocyte, CG17603, TAF[[II]], surveillance, malignant tumor, morbidity, endemics, Thymus-Dependent Lymphocyte, SmokTcr, Malignant Neoplasms, AGE, Phenotypes, disease, DmelCG17603, T cell, Taf250, Patient, SR3-5, Cells, Dominant negative form of Smok, renin-binding protein, CD4, epidemics, T Cell, T-cell receptor complex, CD8, Neoplasia, TAF230, TAF1falseSomatic mutations associate with clonal expansion of CD8+ T cellsSomatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum in non-malignant T cells is unclear. Here, we examined somatic mutations in CD4+ and CD8+ T cells from 90 patients with hematological and immunological disorders and used T cell receptor (TCR) and single-cell sequencing to link mutations with T cell expansions and phenotypes. CD8+ cells had higher mutation burden than CD4+ cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was higher than synonymous variants in CD8+ T cells, indicating non-random distribution. The non-synonymous VAF in CD8+ T cells strongly correlated with the TCR frequency, but not age. We identified mutated pathways essential for T cell function or recurrently mutated in lymphoid neoplasia. Single-cell sequencing revealed cytotoxic Temra phenotypes of mutated T cells. Our findings suggest that somatic mutations contribute to CD8+ T cell expansions without malignant transformation.2024-04-23 14:29:46EGAS000010076069606EGAD00001012121EGAC00001003458