Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas: An integrated analysis of DNA copy number and gene expression

HIV-infected individuals have a significantly increased risk of developing an aggressive B-cell Non-Hodgkin Lymphoma relative to HIV(-) persons. Due to their aggressive nature, AIDS-related lymphomas (ARL) can also be more difficult to classify. Genetic abnormalities are known to play a significant role in HIV(-) lymphomagenesis. To aid in case classification and identify key pathogenetic events in ARL, we analyzed gene expression data and somatic DNA copy number changes by high-resolution array comparative genomic hybridization in tumors from 20 B-cell derived ARL (B-ARL) patients. Gene expression-based predictors robustly classified the B-ARL cases, distinguishing Burkitt lymphoma and diffuse large B-cell lymphoma, and identifying activated B-cell like and germinal center B-cell like molecular subtypes of diffuse large B-cell lymphoma. Array comparative genomic hybridization analysis revealed 13 recurrent losses and 16 recurrent gains in the B-ARL cases, including gain of 19p13.2 and loss of 16q23, not previously reported in B-ARL. The WWOX tumor suppressor gene was characterized as a candidate gene for the 16q23.1 locus and showed gene silencing or truncated transcript in 9 of 16 cases. These data demonstrate the ability to molecularly classify B-ARL lymphomas by gene expression and identified DNA copy number alterations targeted in B-ARL.