Comparative genomic hybridization of 20 patients with Sézary syndrome. Homo sapiens

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.