KEY TAKEAWAYS
- The study aimed to investigate the genomic alterations distinguishing EBV-positive from EBV-negDLBCL to understand their clinical significance and potential treatment implications.
- Researchers noticed that EBV-pos and EBV-neg DLBCL have distinct genetic changes, emphasizing the c-MET and PD-L1/c-Myc pathways as prospective therapeutic targets for additional clinical exploration.
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV-posDLBCL) is an aggressive B-cell lymphoma often mirroring the morphological and immune phenotype characteristics of EBV-negative DLBCL (EBV-negDLBCL).
Fang Liu and the team aimed to assess the clinical relevance of these genomic alterations and identify potential therapeutic targets for improving treatment outcomes in EBV-posDLBCL patients.
To better understand their differences in their genomic landscape, EBV-posDLBCL and EBV-negDLBCL were subjected to whole exome sequencing (WES) and complementary analysis.
About17 new mutation signatures (unknown) 29 signatures (smoking) were revealed in EBV-posDLBCL and 24 specific mutation signatures (aflatoxin associated) in EBV-negDLBCL.
Notably, compared with EBV-negDLBCL, EBV-posDLBCL exhibited a higher frequency of somatic copy number alterations (CNAs) and deletions (P = 0.01). Specifically detected in EBV-posDLBCL were gains at 9p24.1 (PDL1 and JAK2), 8q22.2-q24.23 (DEPTOR and MYC), and 7q31.31-q32.2 (MET).
Overall, 53.7% (22/41) and 62.9% (22/35) of the cases expressed PD-L1 and c-MET, respectively, in neoplastic cells, whereas only 15.4% (4/26) expressed c-MYC. Neoplastic c-MET expression was positively correlated with PD-L1 (P < 0.001) and MYC expression (P = 0.016).
However, no differences in overall survival were observed between positive and negative cases for PD-L1, c-MET, or c-MYC in EBV-posDLBCL. Analysis also showed no difference in tumor mutant burden distribution between EBV-posDLBCL and EBV-negDLBCL (P = 0.41).
Recurrent mutations in EBV-posDLBCL implicated genes such as DCAF8L1, KLF2, and NOL9, while in EBV-negDLBCL, ANK2, BPTF, and CNIH3 were more frequently mutated. Notably, PIM1 emerged as the most altered gene among all WES-detected cases.
The study concluded that genomic alterations significantly differ between EBV-posDLBCL and EBV-negDLBCL, with new genetic variations identified in EBV-posDLBCL. The positive correlation between c-MET and PD-L1/c-Myc expression suggests their potential involvement in EBV-posDLBCL pathogenesis, warranting prospective exploration in MET-directed therapy trials.
The study was funded by the Foshan Science Technology and Medical Foundation, 14th Five-year high level specialty construction project in Foshan and Special fund of Foshan Summit plan.
Source: https://pubmed.ncbi.nlm.nih.gov/38457199/
Liu F, Tian S, Liu Q, et al. (2024). “Comparison of genomic alterations in Epstein-Barr virus-positive and Epstein-Barr virus-negative diffuse large B-cell lymphoma.” Cancer Med. 2024 Feb;13(4):e6995. doi: 10.1002/cam4.6995. PMID: 38457199; PMCID: PMC10922027.
