Molecularly heterogeneous disease with multiple complex chromosomal translocations and genetic abnormalities as identified by cytogenetics and gene expression profiling.
Disease is derived from B cells that have undergone somatic mutation in the immunoglobulin (Ig) genes.
BCL6 gene rearrangements may be specific for DLBCL.
— Approximately 40 percent of cases in immunocompetent persons and approximately 20 percent of HIV-related cases display BCL6 rearrangements.
— BCL6 protein mediates the specific binding of several transcription factors to DNA.
Approximately 30 percent of patients have the t(14;18) translocation involving BCL2 and the Ig-heavy-chain gene.
— The presence of p53 mutation in combination with BCL2 denotes that the tumor is derived from a transformation of a prior follicular lymphoma.
Aberrant somatic mutation occurs in more than 50 percent of cases and targets multiple loci (e.g., IGH, PIM1, MYC, RhoH/TTF (ARHH), PAX5, c-MYC).
Three molecular subtypes have been identified determined by gene expression profiling:
— Germinal center B-like (GCB): arise from normal germinal center B cells.
— Activated B-cell-like (ABC): may arise from postgerminal center B cells that are arrested during plasmacytic differentiation.
— Primary mediastinal B-cell lymphoma: might arise from thymic B cells.