Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling
Ralf Küppers, … , Martin-Leo Hansmann, Riccardo Dalla-Favera
Ralf Küppers, … , Martin-Leo Hansmann, Riccardo Dalla-Favera
Published February 15, 2003
Citation Information: J Clin Invest. 2003;111(4):529-537. https://doi.org/10.1172/JCI16624.
View: Text | PDF
Article Oncology Article has an altmetric score of 6

Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling

Abstract

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.

Authors

Ralf Küppers, Ulf Klein, Ines Schwering, Verena Distler, Andreas Bräuninger, Giorgio Cattoretti, Yuhai Tu, Gustavo A. Stolovitzky, Andrea Califano, Martin-Leo Hansmann, Riccardo Dalla-Favera

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Identification of genes differentially expressed between HL lines, LCL, ...
Identification of genes differentially expressed between HL lines, LCL, and ABC-type DLCL lines versus BL and GC-type DLCL. The gene expression profiles of four HL, five LCL, and two ABC-type DLCL lines that clustered together in the unsupervised analysis (see Figure 1) were compared with those generated from six BL and six DLCL (non–ABC-type) cell lines by supervised hierarchical clustering using Genes@Work (see Methods). Columns represent individual cell lines, and rows correspond to genes. Color changes within a row indicate expression relative to the average of the sample population. Values are quantified by the scale bar that visualizes the difference in the ζ-score (expression difference/SD) relative to the mean. Genes are ranked based on the z-score (mean expression difference of the respective gene between phenotype and control group/SD). The support value for supervised analysis was chosen as n = n0 – 1, where n0 is the number of cells in the given phenotype set, allowing for one unclustered sample per pattern in the phenotype set. The corresponding expression data for BCL-2 and BCL-6 were obtained by relaxing the criteria in the supervised clustering and are therefore shown separately at the bottom. Gene names and cell lines are indicated.