title: AID is expressed in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas and is not correlated with intraclonal heterogeneity.
abstract: Activation-induced cytidine deaminase (AID), highly expressed in germinal center (GC)-lymphocytes, is involved in somatic hypermutation (SHM). We examined AID expression in diffuse large B-cell lymphomas (DLBCL) of germinal center B-cell (GCB)-like and activated B-cell (ABC)-like subtypes. These two types of DLBCL are characterized by high and low expression of GC-specific genes, respectively. AID expression was detected in both GCB- and ABC-like DLBCL, thus demonstrating a dissociation between AID expression and that of other GC genes. We also tested for the presence of intraclonal heterogeneity in immunoglobulin and BCL6 genes in those same tumors and in follicle center lymphomas (FCL) that transformed to DLBCL. The level of AID expression did not correlate with the presence of intraclonal sequence heterogeneity in either IgV(H) or BCL6. Our findings suggest that lymphomas maintain some but not all of the gene expression signatures of their normal B-cell counterparts. The fact that AID expression can be elevated without intraclonal sequence heterogeneity raises the possibility that other factors are required for SHM in these tumors. We found decreased levels of AID expression in DLBCL that evolved from FCL and which had acquired new mutations in their BCL6 genes. This dissociation suggests that AID expression and SHM may occur at the time prior to the clinical detection of transformed lymphoma.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA. ilossos@med.miami.edu <ilossos@med.miami.edu>
authors.forename: I S
authors.initials: IS
authors.lastname: Lossos
authors.forename: R
authors.initials: R
authors.lastname: Levy
authors.forename: A A
authors.initials: AA
authors.lastname: Alizadeh
mesh_terms: D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D018858:Germinal Center / Q000201:enzymology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000201:enzymology* / Q000235:genetics; D008224:Lymphoma, Follicular / Q000201:enzymology / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051560:Proto-Oncogene Proteins c-bcl-6; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase