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

Karen E. Deffenbacher, Javeed Iqbal, Zhongfeng Liu, Kai Fu, Wing C. Chan

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18-26
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume54
Issue number1
DOIs
StatePublished - May 1 2010

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AIDS-Related Lymphoma
B-Lymphocytes
Gene Expression
DNA
Comparative Genomic Hybridization
Lymphoma, Large B-Cell, Diffuse
HIV
DNA Copy Number Variations
Germinal Center
Burkitt Lymphoma
Gene Silencing
B-Cell Lymphoma
Tumor Suppressor Genes
Non-Hodgkin's Lymphoma
Lymphoma

Keywords

  • AIDS-related lymphoma
  • Array-based comparative genomic hybridization
  • Burkitt lymphoma
  • Diffuse Large B-Cell lymphoma
  • Gene expression profiling

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas : An integrated analysis of DNA copy number and gene expression. / Deffenbacher, Karen E.; Iqbal, Javeed; Liu, Zhongfeng; Fu, Kai; Chan, Wing C.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 54, No. 1, 01.05.2010, p. 18-26.

Research output: Contribution to journalArticle

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