title: STAT3 targets suggest mechanisms of aggressive tumorigenesis in diffuse large B-cell lymphoma.
abstract: The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that, when dysregulated, becomes a powerful oncogene found in many human cancers, including diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma is the most common form of non-Hodgkin's lymphoma and has two major subtypes: germinal center B-cell-like and activated B-cell-like. Compared with the germinal center B-cell-like form, activated B-cell-like lymphomas respond much more poorly to current therapies and often exhibit overexpression or overactivation of STAT3. To investigate how STAT3 might contribute to this aggressive phenotype, we have integrated genome-wide studies of STAT3 DNA binding using chromatin immunoprecipitation-sequencing with whole-transcriptome profiling using RNA-sequencing. STAT3 binding sites are present near almost a third of all genes that differ in expression between the two subtypes, and examination of the affected genes identified previously undetected and clinically significant pathways downstream of STAT3 that drive oncogenesis. Novel treatments aimed at these pathways may increase the survivability of activated B-cell-like diffuse large B-cell lymphoma.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hardee
authors.forename: Zhengqing
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.forename: Philippe
authors.initials: P
authors.lastname: Lacroute
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: cancer signaling; genomics; next-generation sequencing; oncogenic pathways; signal transduction