Reed-Sternberg cell genome expression supports a B-cell lineage

The malignant Reed-Sternberg cell of Hodgkin's disease, first described a c entury ago, has resisted in-depth analysis due to its extreme rarity in lym phomatous tissue. To directly study its genome-wide gene expression, approx imately 11,000,000 bases (27,518 cDNA sequences) of expressed gene sequence was determined from living single Reed-Sternberg cells, Hodgkin's tissue, and cell lines. This approach increased the number of genes known to be exp ressed in Hodgkin's disease by 20-fold to 2,666 named genes. The data here indicate that Reed-Sternberg cells from both nodular sclerosing and lymphoc yte predominant Hodgkin's disease were derived from an unusual B-cell linea ge based on a comparison of their gene expression to approximately 40,000,0 00 bases (10(5) sequences) of expressed gene sequence from germinal center B cells (GCB) and dendritic cells. The data set of expressed genes, reporte d here and on the World Wide Web, forms a basis to understand the genes res ponsible for Hodgkin's disease and develop novel diagnostic markers and the rapies. This study of the rare Reed-Sternberg cell, concealed in its hetero genous cellular context, also provides a formidable test case to advance th e limit of analysis of differential gene expression to the single disease c ell. (C) 1999 by The American Society of Hematology.