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STAT3 targets suggest mechanisms of aggressive tumorigenesis in diffuse large B-cell lymphoma.

Hardee J, Ouyang Z, Zhang Y, Kundaje A, Lacroute P, Snyder M - G3 (Bethesda) (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305.

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.

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RNA-Seq gene enrichment for ontological categories. Scale is the –log10(P-value) of the binomial P-value, equivalent to the exponent. All enriched GO Biological Processes categories are shown, P < 0.05.
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fig7: RNA-Seq gene enrichment for ontological categories. Scale is the –log10(P-value) of the binomial P-value, equivalent to the exponent. All enriched GO Biological Processes categories are shown, P < 0.05.

Mentions: Genes with GO BP categories related to cell adhesion, motility, and chemotaxis are enriched in ABC DLBCL cells relative to GCB cells (Figure 7). The expression of these pathways would prime tumors to spread rapidly from their lymph nodes of origin, and may partially explain why ABC lymphomas are so much more aggressive than their GCB counterparts.


STAT3 targets suggest mechanisms of aggressive tumorigenesis in diffuse large B-cell lymphoma.

Hardee J, Ouyang Z, Zhang Y, Kundaje A, Lacroute P, Snyder M - G3 (Bethesda) (2013)

RNA-Seq gene enrichment for ontological categories. Scale is the –log10(P-value) of the binomial P-value, equivalent to the exponent. All enriched GO Biological Processes categories are shown, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852380&req=5

fig7: RNA-Seq gene enrichment for ontological categories. Scale is the –log10(P-value) of the binomial P-value, equivalent to the exponent. All enriched GO Biological Processes categories are shown, P < 0.05.
Mentions: Genes with GO BP categories related to cell adhesion, motility, and chemotaxis are enriched in ABC DLBCL cells relative to GCB cells (Figure 7). The expression of these pathways would prime tumors to spread rapidly from their lymph nodes of origin, and may partially explain why ABC lymphomas are so much more aggressive than their GCB counterparts.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305.

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.

Show MeSH
Related in: MedlinePlus