Maguire A, et al. - In view of the observation that human immunodeficiency virus (HIV) infected (+) individuals are up to 17-fold more likely to experience diffuse large B cell lymphoma (DLBCL) with a more aggressive clinical course and frequently present with advanced stages compared to HIV negative (-) individuals, researchers performed this retrospective study examining HIV(+) and HIV(-) germinal center B-cell (GCB) DLBCL cases for the molecular pathology underpinning the clinical features. They used digital gene expression analysis, array comparative genomic hybridization (CGH) and immunohistochemistry (IHC) for determining the transcriptional, genomic, and protein expression differences. HIV(+) GCB-DLBCL tumors had significantly increased genes associated with cell cycle progression (CCNA2, CCNB1, CDC25A, E2F1), DNA replication (MCM2, MCM4, MCM7) and DNA damage repair, including 8 Fanconi Anemia genes (FANCA, FANCD1/BRCA2, FANCE, FANCG, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCV/MAD2L2), compared to HIV(-) tumors. In contrast, the HIV(+) cohort showed significantly decreased genes associated with cell cycle inhibition (CDKN1A, CDKN1B) as well as apoptosis regulating BCL2 family members (BCL2, BAX, BIM, BMF, PUMA). As per array CGH data, fewer copy number variations were there in HIV(+) GCB-DLBCL tumors than their HIV(-) counterparts, showing enhanced genomic stability. HIV(+) GCB-DLBCL is thus identified to be a distinct molecular malignancy from HIV(-) GCB-DLBCL. Ki67 IHC staining confirmed its increased proliferative capacity. It has enhanced genomic stability which is likely related to the enhanced expression of DNA repair genes.