EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic...

Area of Science:

• Oncology
• Virology
• Genetics

Background:

• The molecular basis of posttransplant diffuse large B cell lymphoma (PT-DLBCL) remains unclear.
• Epstein-Barr virus-positive (EBV+) and EBV-negative (EBV-) PT-DLBCL exhibit distinct gene expression profiles.
• EBV-negative PT-DLBCL transcriptomes resemble those of DLBCL in immunocompetent individuals (IC-DLBCL).

Purpose of the Study:

• To validate transcriptomic findings at the genomic level.
• To compare genomic profiles of EBV+ PT-DLBCL, EBV- PT-DLBCL, and IC-DLBCL.
• To elucidate the distinct pathogenesis of EBV+ and EBV- PT-DLBCL.

Main Methods:

• Array-comparative genome hybridization (aCGH) was performed on 21 EBV+ PT-DLBCL, 6 EBV- PT-DLBCL, and 11 IC-DLBCL samples.
• Genomic and transcriptomic data were integrated for comprehensive analysis.
• Recurrent genomic imbalances were identified and compared across cohorts.

Main Results:

• EBV+ and EBV- PT-DLBCL possess distinct aCGH profiles with minimal overlap.
• EBV- PT-DLBCL showed at least 10 aberrations common to IC-DLBCL, including gains of 3/3q, 18q, and losses of 6q23/TNFAIP3 and 9p21/CDKN2A.
• The most frequent aberration in EBV+ PT-DLBCL was gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2.
• FOXP1 and CDKN2A were not critical in EBV+ PT-DLBCL pathogenesis.

Conclusions:

• Genomic profiling confirms EBV- and EBV+ PT-DLBCL are distinct entities.
• EBV- PT-DLBCL shares significant genomic similarities with IC-DLBCL.
• These findings support the hypothesis that EBV- PT-DLBCL arises de novo in transplant recipients.