Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Diffuse large B-cell lymphoma (DLBCL) has significant treatment failure rates.
• Early relapse (ER) after first-line therapy portends a poorer prognosis than late relapse (LR).
• Understanding genomic drivers of relapse timing is crucial for improved patient outcomes.

Purpose of the Study:

• To identify copy number variations (CNVs) associated with early versus late relapse in DLBCL.
• To explore the distinct genomic landscapes of ER and LR DLBCL.
• To uncover potential therapeutic targets based on relapse-specific CNVs.

Main Methods:

• Analysis of 39 DLBCL tumor samples from the CORAL prospective study.
• Utilized Significance Analysis of Microarrays (SAM) for identifying differentially distributed CNVs.
• Controlled for false positives using a permutation-based method and a false discovery rate < 0.05.

Main Results:

• Frequent deletions of CDKN2A/B (28%) and IBTK (23%) were observed in relapsed DLBCL.
• Identified 56 protein-coding genes and 25 long non-coding RNAs with differential CNVs between ER and LR.
• ER DLBCLs showed CNVs related to transcription regulation, cell cycle, and apoptosis (e.g., histone H1T duplications).
• LR DLBCLs exhibited CNVs linked to immune response and cell proliferation (e.g., B2M deletions, HES1 duplications).

Conclusions:

• Distinct CNV profiles characterize early and late relapses in DLBCL.
• Genomic aberrations in ER DLBCLs are associated with cell cycle and apoptosis pathways.
• Genomic aberrations in LR DLBCLs are linked to immune response and proliferation pathways.
• These findings suggest potential for pathway-targeted therapies tailored to ER and LR DLBCL.