Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma.

ABSTRACT: Enteropathy-associated intestinal T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) have distinctive clinical context, morphology, and immunophenotype. To characterize their genetic and molecular specificities, we compared 30 EATLs and 52 MEITLs by whole-exome, RNA and miRNA sequencing and DNA methylation profiling. Highly recurrent SETD2 loss-of-function alterations and frequent mutations of H3-3A/B consistently altering H3R2, implying deregulation of histone marks, were selectively found in MEITL. EATL instead harbored frequent mutations in TET2, ARID1A, and KMT2D. Highly prevalent JAK-STAT pathway mutations preferentially affected JAK3 and STAT5B in MEITL, and JAK1 and STAT3 in EATL. Half of EATLs contained disruptive mutations in HLA class I gene

SUBMITTER: Vallois D 

PROVIDER: S-EPMC12789032 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature