Genome wide DNA-profiling of HIV-related B-cell lymphomas.
Non-Hodgkin lymphomas (NHL) represent a frequent complication of human immunodeficiency virus (HIV) infection. To elucidate HIV-NHL pathogenesis, we performed a genome-wide DNA profiling based on a single nucleotide polymorphism-based microarray comparative genomic hybridization in 57 HIV-lymphomas and, for comparison, in 105 immunocompetent diffuse large B-cell lymphomas (IC-DLBCL). Genomic complexity varied across HIV-NHL subtypes. HIV-Burkitt lymphoma showed a significantly lower number of lesions than HIV-DLBCL (P = 0.032), whereas the median number of copy number changes was significantly higher in Epstein-Barr virus negative (EBV-) HIV-DLBCL (42.5, range 8-153) compared to EBV+ cases (22; range 3-41; P = 0.029). Compared to IC-DLBCL, HIV-DLBCL displayed a distinct genomic profile with no gains of 18q and specific genetic lesions. Fragile sites-associated genes, including FHIT (FRA3B), WWOX (FRA16D), DCC (FRA18B) and PARK2 (FRA6E) were frequently inactivated in HIV-NHL by interstitial deletions, and a significantly higher prevalence of FHIT alterations was observed in HIV-DLBCL compared to IC-DLBCL. The same genes involved by fragile site deletions were also frequently affected by aberrant methylation of regulative regions.
Capello
Daniela
D
Department of Clinical and Experimental Medicine & BRMA, "Amedeo Avogadro" University of Eastern Piedmont, Novara, Italy.
Scandurra
Marta
M
Poretti
Giulia
G
Rancoita
Paola M V
PM
Mian
Michael
M
Gloghini
Annunziata
A
Deambrogi
Clara
C
Martini
Maurizio
M
Rossi
Davide
D
Greiner
Timothy C
TC
Chan
Wing C
WC
Ponzoni
Maurilio
M
Moreno
Santiago M
SM
Piris
Miguel A
MA
Canzonieri
Vincenzo
V
Spina
Michele
M
Tirelli
Umberto
U
Inghirami
Giorgio
G
Rinaldi
Andrea
A
Zucca
Emanuele
E
Favera
Riccardo D
RD
Cavalli
Franco
F
Larocca
Luigi Maria
LM
Kwee
Ivo
I
Carbone
Antonino
A
Gaidano
Gianluca
G
Bertoni
Francesco
F
D002051:Burkitt Lymphoma / Q000235:genetics; D002869:Chromosome Aberrations; D019175:DNA Methylation; D005787:Gene Frequency; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D046228:Microarray Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide