The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.
Overall design
During this study we analyzed 20 patients with Sézary syndrome by array-based comparative genomic hybridization (array CGH). Initial array CGH was done by means of a submegabase resolution BAC array (GPL5114; 17 samples). Aberrations encompassing chromosome arm 19p were verified and fine-mapped by hybridizations onto a whole genome 400k (GPL9777; 14 samples) and a customized oligonucleotide array (GPL10304; 3 samples), respectively. FISH analyses were used for further verification.
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