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- W3128307790 abstract "Enteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of coeliac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis.Pure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridisation and RNA sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=18) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines.80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors, and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines.Mutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NF-κB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL." @default.
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- W3128307790 date "2021-02-12" @default.
- W3128307790 modified "2023-10-16" @default.
- W3128307790 title "Oncogenetic landscape of lymphomagenesis in coeliac disease" @default.
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- W3128307790 cites W1980839459 @default.
- W3128307790 cites W1991473719 @default.
- W3128307790 cites W1998839233 @default.
- W3128307790 cites W2002774826 @default.
- W3128307790 cites W2010220327 @default.
- W3128307790 cites W2031643141 @default.
- W3128307790 cites W2067637255 @default.
- W3128307790 cites W2073385776 @default.
- W3128307790 cites W2078376874 @default.
- W3128307790 cites W2079683856 @default.
- W3128307790 cites W2081107312 @default.
- W3128307790 cites W2085655145 @default.
- W3128307790 cites W2086217304 @default.
- W3128307790 cites W2107470925 @default.
- W3128307790 cites W2109792437 @default.
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- W3128307790 cites W2516341826 @default.
- W3128307790 cites W2523679195 @default.
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- W3128307790 cites W2601320624 @default.
- W3128307790 cites W2618558825 @default.
- W3128307790 cites W2718751133 @default.
- W3128307790 cites W2752969927 @default.
- W3128307790 cites W2773899764 @default.
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- W3128307790 doi "https://doi.org/10.1136/gutjnl-2020-322935" @default.
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