Tumor-specific and proliferation-specific gene expression typifies murine transgenic B cell lymphomagenesis.
The dual bromodomain protein Brd2 is closely related to the basal transcription factor TAF(II)250, 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.
Lenburg
Marc E
ME
Department of Genetics and Genomics, and Boston University School of Medicine, Boston, Massachusetts 02118.
Sinha
Anupama
A
Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118.
Faller
Douglas V
DV
Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118.
Denis
Gerald V
GV
Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118. Electronic address: gdenis@bu.edu.
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D015973:Gene Expression Regulation, Leukemic; D052138:Genes, Neoplasm; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D035362:Transcription Factor TFIID / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D017346:Protein Serine-Threonine Kinases; D035362:Transcription Factor TFIID; D014157:Transcription Factors; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins