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Journal of Histochemistry and Cytochemistry, Vol. 49, 799-800, June 2001, Copyright © 2001, The Histochemical Society, Inc.

BRIEF REPORT

Gene Expression Analysis of Single Neoplastic Cells and the Pathogenesis of Hodgkin's Lymphoma

Jeffrey Cossmana
a Department of Pathology, Georgetown University Medical Center, Washington, DC

Correspondence to: Jeffrey Cossman, Oscar Benwood Hunter Professor of Pathology, Georgetown U. Medical Center, NW 103 Medical–Dental Building, 3900 Reservoir Rd. NW, Washington, DC 20007.

The origin of the Reed–Sternberg cell of Hodgkin's disease remained clouded in mystery for almost a century after its discovery in 1898. The major obstacle to its understanding is that, unlike other cancers, the malignant cell of Hodgkin's disease is vastly outnumbered by surrounding non-neoplastic cells at approximately 1000:1. We have devised several strategies to isolate Reed–Sternberg T-cells to determine their origin, global gene expression and, ultimately, their pathogenesis. This has increased the number of genes known to be expressed in Reed–Sternberg cells by >100-fold to over 12,000. Approaches such as density gradients, microdissection, and cell sorting help to enrich Reed–Sternberg cells for genomic DNA analysis. However, single-cell micromanipulation of living Reed–Sternberg cells was required to determine the genome-wide gene expression profile of these cells. Combined analysis of single cells and cell lines revealed the expression of 2666 named genes. Further analysis with high-density gene expression microarrays has demonstrated the expression of approximately 12,000 genes by Reed–Sternberg cells. The gene expression profile is that of an aberrant germinal center B-lymphocyte that resists apoptosis through CD40 signaling and NF{kappa}B activation. Gene expression analysis of Hodgkin's disease is an extreme test case demonstrating the application of high-throughput gene expression studies even to individual cells from clinical samples. (J Histochem Cytochem 49:799–800, 2001)

Key Words: Hodgkin's disease, Reed–Sternberg cells, gene expression, B-lymphocyte


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