Global correlation of genome and transcriptome changes in classical Hodgkin lymphoma.
To identify genes involved in the pathogenesis of classical Hodgkin lymphoma (cHL), we performed serial analysis of gene expression (SAGE) and array-based comparative genomic hybridization (aCGH). Comparison of SAGE libraries of cHL cell lines L428 and L1236 with that of germinal centre B cells revealed consistent overexpression of only 14 genes. In contrast, 141 genes were downregulated in both cHL cell lines, including many B cell and HLA genes. aCGH revealed gain of 2p, 7p, 9p, 11q and Xq and loss of 4q and 11q. Eighteen percent of the differentially expressed genes mapped to regions with loss or gain and a good correlation was observed between underexpression and loss or overexpression and gain of DNA. Remarkably, gain of 2p and 9p did not correlate with increased expression of the proposed target genes c-REL and JAK2. Downregulation of many genes within the HLA region also did not correlate with loss of DNA. FSCN1 and IRAK1 mapping at genomic loci (7p and Xq) that frequently showed gain were overexpressed in cHL cell lines and might be involved in the pathogenesis of cHL.
Kluiver
Joost
J
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Kok
Klaas
K
Pfeil
Ines
I
de Jong
Debora
D
Blokzijl
Tjasso
T
Harms
Geert
G
van der Vlies
Pieter
P
Diepstra
Arjan
A
Atayar
Ciğdem
C
Poppema
Sibrand
S
Küppers
Ralf
R
van den Berg
Anke
A
D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D052138:Genes, Neoplasm / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D006689:Hodgkin Disease / Q000209:etiology / Q000235:genetics*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D015854:Up-Regulation
D002352:Carrier Proteins; C502658:FSCN1 protein, human; D006680:HLA Antigens; D008840:Microfilament Proteins; D020569:Proto-Oncogene Proteins c-rel; D012334:RNA, Neoplasm; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases