Reed-Sternberg cell genome expression supports a B-cell lineage.
The malignant Reed-Sternberg cell of Hodgkin's disease, first described a century ago, has resisted in-depth analysis due to its extreme rarity in lymphomatous tissue. To directly study its genome-wide gene expression, approximately 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 expressed 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 lymphocyte predominant Hodgkin's disease were derived from an unusual B-cell lineage based on a comparison of their gene expression to approximately 40,000,000 bases (10(5) sequences) of expressed gene sequence from germinal center B cells (GCB) and dendritic cells. The data set of expressed genes, reported here and on the World Wide Web, forms a basis to understand the genes responsible for Hodgkin's disease and develop novel diagnostic markers and therapies. This study of the rare Reed-Sternberg cell, concealed in its heterogenous cellular context, also provides a formidable test case to advance the limit of analysis of differential gene expression to the single disease cell.
Cossman
J
J
Georgetown University Medical Center, Washington, DC, USA. cossmanj@gunet.georgetown.edu
Annunziata
C M
CM
Barash
S
S
Staudt
L
L
Dillon
P
P
He
W W
WW
Ricciardi-Castagnoli
P
P
Rosen
C A
CA
Carter
K C
KC
D001402:B-Lymphocytes / Q000473:pathology*; D002454:Cell Differentiation; D019070:Cell Lineage; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D020224:Expressed Sequence Tags; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D018858:Germinal Center / Q000166:cytology; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm