Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling.
Hodgkin lymphoma (HL) is a malignancy of unknown pathogenesis. The malignant Hodgkin and Reed/Sternberg (HRS) cells derive from germinal center B cells (or rarely, T cells) but have a heterogeneous and largely uncharacterized phenotype. Using microarrays, we compared the gene expression profile of four HL cell lines with profiles of the main B cell subsets and B cell non-HLs to find out whether HRS cells, despite their described heterogeneity, show a distinct gene expression, to study their relationship to other normal and malignant B cells, and to identify genes aberrantly or overexpressed by HRS cells. The HL lines indeed clustered as a distinct entity, irrespective of their B or T cell derivation, and their gene expression was most similar to that of EBV-transformed B cells and cell lines derived from diffuse large cell lymphomas showing features of in vitro-activated B cells. Twenty-seven genes, most of which were previously unknown to be expressed by HRS cells, showed aberrant expression specifically in these cells, e.g., the transcription factors GATA-3, ABF1, EAR3, and Nrf3. For five genes, expression in primary HRS cells was confirmed. The newly identified HL-specific genes may play important roles in the pathogenesis of HL, potentially represent novel diagnostic markers, and can be considered for therapeutic targeting.
Küppers
Ralf
R
Institute for Genetics, and. Department of Internal Medicine I, University of Cologne, Cologne, Germany. ralf.kuppers@uni-koeln.de
Klein
Ulf
U
Schwering
Ines
I
Distler
Verena
V
Bräuninger
Andreas
A
Cattoretti
Giorgio
G
Tu
Yuhai
Y
Stolovitzky
Gustavo A
GA
Califano
Andrea
A
Hansmann
Martin-Leo
ML
Dalla-Favera
Riccardo
R
D001402:B-Lymphocytes / Q000821:virology; D001483:Base Sequence; D002472:Cell Transformation, Viral; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D009857:Oncogenes; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004273:DNA, Neoplasm