This molecularly heterogeneous disease with multiple complex chromosomal translocations and genetic abnormalities is 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% of cases in immunocompetent persons and approximately 20% of human immunodeficiency virus (HIV)-related cases display BCL6 rearrangements.
— BCL6 protein mediates the specific binding of several transcription factors to DNA.
Approximately 30% 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% of cases and targets multiple loci (eg, 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 (Table 60–2).
— Activated B-cell–like (ABC) may arise from postgerminal center B cells that are arrested during plasmacytic differentiation (see Table 60–2...