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J. Biol. Chem., Vol. 282, Issue 7, 4803-4811, February 16, 2007

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Tumor-specific and Proliferation-specific Gene Expression Typifies Murine Transgenic B Cell Lymphomagenesis^*

Marc E. Lenburg, Anupama Sinha, Douglas V. Faller, and Gerald V. Denis¹

From the Department of Genetics and Genomics, and Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118

The dual bromodomain protein Brd2 is closely related to the basal transcription factor TAF_II250, which is essential for cyclin A transactivation and mammalian cell cycle progression. In transgenic mice, constitutive lymphoid expression of Brd2 causes a malignancy most similar to human diffuse large B cell lymphoma. We compare the genome-wide transcriptional expression profiles of these lymphomas with those of proliferating and resting normal B cells. Transgenic tumors reproducibly show differential expression of a large number of genes important for cell cycle control and lymphocyte biology; expression patterns are either tumor-specific or proliferation-specific. Several of their human orthologs have been implicated in human lymphomagenesis. Others correlate with human disease survival time. BRD2 is underexpressed in some subtypes of human lymphoma and these subtypes display a number of similarities to the BRD2-mediated murine tumors. We illustrate with a high degree of detail that cancer is more than rampant cellular proliferation, but involves the additional transcriptional mobilization of many genes, some of them poorly characterized, which show a tumor-specific pattern of gene expression.

Received for publication, June 19, 2006 , and in revised form, October 27, 2006.

^* This work was supported in part by United States Public Health Service Grants CA75107 and CA102889 (to G. V. D.) from the NCI, National Institutes of Health and RSG05072-LIB (to G. V. D.) from the American Cancer Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and File 1.

¹ To whom correspondence should be addressed: Cancer Research Center, Rm. K521, Boston University School of Medicine, 80 East Concord St., Boston, MA 02118. Tel.: 617-414-1371; Fax: 617-638-5673; E-mail: gdenis{at}bu.edu.

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