Functional Consequences of Chromosomal Alterations in Angioimmunoblastic T-Cell Lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of non-Hodgkin's lymphoma, representing a significant portion of peripheral T-cell lymphomas (PTCL). To elucidate the genomic landscape of PTCL, comprehensive genomic analysis was performed on 25 AITL and 19 PTCL- not otherwise specified (NOS) cases. Our findings reveal distinct genetic alterations in AITL, including a lower mutation burden and an enrichment of reactive oxygen species (ROS)-associated mutational signature (SBS18) when compared to PTCL-NOS. Besides recurrent somatic mutations in TET2 and RhoA, we have discovered frequent novel focal deletion on chromosome 8q24.21, impacting the PVT1 gene. Functional characterization demonstrated that this deletion activates the DNA damage pathway via CDKN1A/p21, potentially conferring a survival advantage to AITL cells under DNA damaging stress. These findings shed light on the molecular mechanisms underlying AITL development and highlight the potential clinical implications of chr8q24.21 focal deletion in this disease. Further studies with larger cohorts are warranted to validate these findings and explore their therapeutic implications.

Chan:SymBio Pharmaceuticals: Research Funding.