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- W4285992248 abstract "Chronic T-cell antigen stimulation has long been suggested to contribute to carcinogenesis in mycosis fungoides (MF), but evidence of this phenomenon is lacking at the genetic level. Furthermore, mutations that alter malignant T-cells’ antigen specificities have not been previously described in MF. Here, we report evidence from two patients whereby the presence of single base substitutions (SBS) in the antigen-binding regions of the malignant clones’ T-cell receptors (TCR) coincide with changes in clinical behavior. A review of longitudinal high-throughput sequencing data obtained from lesional skin biopsies identified two patients with unique SBS in the antigen-binding region of malignant T-cell clones. In all biopsies, each predominant TCRβ clone encoded an uninterrupted chain of amino acids. While the SBS in both cases resulted in a single amino acid change, the V, D, and J family gene assignments remained identical. These observations imply mutations altering the antigen specificities of the malignant clones. The mutations coincided with different clinical and pathological behavior in both cases, including new-onset tumor formation with large cell transformation in the first case, and resistance to localized radiation and topical treatment in the second case. Furthermore, all deducted SBS mutations were identified within the ultraviolet (UV) signature according to the COSMIC Mutational Signatures collaboration. These cases provide evidence for UV-induced alterations in the antigen-binding regions of the malignant TCRs that parallel clinical and histological progressions in MF. Our observations can generate hypotheses about the role of stimulation by antigen in lymphomagenesis." @default.
- W4285992248 created "2022-07-21" @default.
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- W4285992248 date "2022-08-01" @default.
- W4285992248 modified "2023-09-28" @default.
- W4285992248 title "109 Mutations in the T-cell receptor antigen-binding region of malignant cells in mycosis fungoides coincide with clinical and histological progression" @default.
- W4285992248 doi "https://doi.org/10.1016/j.jid.2022.05.044" @default.
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