Genomic and epigenomic co-evolution in follicular lymphomas

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Follicular lymphoma (FL) with t(14;18) is a recurrent B-cell neoplasm.
• Understanding its clonal evolution is crucial for treatment strategies.

Purpose of the Study:

• To investigate the clonal evolution of non-transformed t(14;18)-positive FL using paired primary and relapse samples.
• To identify genetic and epigenetic alterations driving tumor evolution and co-evolution.

Main Methods:

• Phylogenetic reconstruction using immunoglobulin heavy chain (IGH) gene rearrangements and somatic hypermutation (SHM).
• Targeted sequencing of driver genes and SHM-affected loci.
• Genome-wide chromosomal imbalance and DNA methylation analysis.

Main Results:

• Observed a spectrum of evolutionary patterns, from minimal to divergent evolution.
• Demonstrated ongoing SHM and counter-selection of mutations affecting B-cell receptor (BCR) conformation.
• Found a correlation between evolutionary divergence across genetic and epigenetic levels, suggesting co-evolution.

Conclusions:

• CREBBP and AID may act as modifiers of genetic and epigenetic co-evolution in FL.
• Insights into FL evolution can inform future therapeutic approaches.