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.
Deffenbacher
Karen E
KE
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
Iqbal
Javeed
J
Liu
Zhongfeng
Z
Fu
Kai
K
Chan
Wing C
WC
D000328:Adult; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D003937:Diagnosis, Differential; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000175:diagnosis* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult