Our results identify AICDA as a driver of epigenetic heterogeneity in B-cell lymphomas with potential significance for other tumors with aberrant expression of cytidine deaminases.
No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression.
Epstein-Barr virus latent membrane protein 1 increases genomic instability through Egr-1-mediated up-regulation of activation-induced cytidine deaminase in B-cell lymphoma.
Activation-induced cytidine deaminase (AID/AICDA) is required for somatic hypermutation and class-switch recombination of the immunoglobulin gene, and for c-myc translocation of germinal center-derived B-cell lymphoma.
In addition to this fundamental role in immune diversification, aberrant targeting of AID activity contributes to point mutations and translocations of oncogenes associated with B-cell lymphoma.
This is an important question because AID is highly mutagenic and is sometimes mistargeted to other highly expressed genes, including proto-oncogenes, leading to B cell lymphomas.
Expression levels of activation-induced cytidine deaminase (AID) which are thought to be associated with occurrence of B-NHL were analyzed in these CHC B cells.
Mature B cell lymphomas arising as a result of deregulated AID expression are phenotypically diverse and harbor clonal reciprocal translocations involving a group of Immunoglobulin (Ig) and non-Ig genes that are direct targets of AID.
Indeed, AID expression is not restricted to GC-derived B-cell lymphomas, but is also found in other types of B-cell lymphoma and even in nonlymphoid tumors, suggesting that ectopically expressed AID is involved in tumorigenesis and disease progression in a wide variety of cell types.
It was seen that EBV infected, AID, and pol-eta expressing B cells accumulated mutations in cellular proto-oncogenes (BCL-6 and p53) that are known to be involved in the genesis of B cell lymphoma.
Deregulation of AID may lead to the aberrant activation or persistence of both genetic processes, thus contributing to the pathogenesis of B-cell lymphomas by mistargeted mutagenesis or recombination.
Primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type, are both targeted by aberrant somatic hypermutation but demonstrate differential expression of AID.
These results indicate that AID expression and ASHM are associated with higher-grade transformation of CLL and provide further evidences that AID expression and ASHM may be activated during the clonal history of B-cell lymphomas.
These results indicate that AID expression and ASHM are associated with higher-grade transformation of CLL and provide further evidences that AID expression and ASHM may be activated during the clonal history of B-cell lymphomas.
AID binds specifically to G-loops within transcribed S regions and c-MYC, and G-loops in c-MYC map to the regions associated with translocation breakpoints and aberrant hypermutation in B-cell lymphomas.
AID expression in vivo is considered to be restricted to germinal center B lymphocytes, yet AID expression is also seen in many B cell lymphomas, hinting at a potential role for the development of these malignancies.