Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T-Cell Lymphoma.

ABSTRACT: Nodal follicular helper T-cell (T _FH) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole-exome sequencing (n = 124), transcriptomic (n = 78), and methylation (n = 40) analysis, we identified recurrent mutations in known epigenetic drivers (TET2, DNMT3A, IDH2 ^R172 ) and novel ones (TET3, KMT2D). TET2, IDH2 ^R172 , DNMT3A co-mutated AITLs had poor prognosis (p < 0.0001). Genes regulating T-cell receptor (TCR) signaling (CD28, PLCG1, VAV1, FYN) or activation (RHOA ^G17V ) or regulators of the PI3K-pathway (PIK(3)C members, PTEN, PHLPP1, PHLPP2) were mutated. CD28 mutation/fusion was associated with poor prognosis (p = 0.02). WES of purified, neoplastic T-cell (CD3⁺PD1⁺) demonstrated high concord

SUBMITTER: Bouska A 

PROVIDER: S-EPMC12326222 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature