Abstract B25: DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation
| Autor: | Davide Pellacani, Vincent M. Mann, Gail P. Risbridger, Mitchell G. Lawrence, Michael J. Stower, Dimitra Kestoras, Matthew S. Simms, Fiona M. Frame, Norman J. Maitland, Paul A. Berry, Alastair Droop, Anne T. Collins |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:B25-B25 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Prostate cancer (CaP) is mostly composed of differentiated luminal cells, but contains a small subpopulation of undifferentiated basal cells (including stem-like cells), which is thought to be the driving force of CaP. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. This study aimed to understand the function and origin of CpG island hypermethylation in CaP, in the context of cancer hierarchy and differentiation. We have analyzed separately primary prostate basal and luminal cells derived from BPH and CaP. This allowed us to dissect the intra-tumor heterogeneity, and to understand the origin of gene downregulation and hypermethylation in CaP. We report that a set of genes commonly hypermethylated in CaP (including GSTP1) is: (i) downregulated as a result of prostate-specific epithelial differentiation in both CaP and benign prostatic hyperplasia (BPH); (ii) selectively hypermethylated in differentiated (luminal) cancer cells, process promoted by the hyperproliferating phenotype of these cells; (iii) actively expressed and methylation free in undifferentiated (basal) CaP cells. Downregulation and hypermethylation of these genes is not essential for tumor development or tumor expansion. Moreover, for all these genes, downregulation induced by prostate-specific differentiation, is independent of DNA hypermethylation, and is associated with detachment of RNA PolII from their promoter and reduction in histone marks associated with active transcription. Citation Format: Davide Pellacani, Dimitra Kestoras, Alastair P. Droop, Fiona M. Frame, Paul A. Berry, Mitchell G. Lawrence, Michael J. Stower, Matthew S. Simms, Vincent M. Mann, Anne T. Collins, Gail P. Risbridger, Norman J. Maitland. DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B25. |
| Databáze: | OpenAIRE |
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