2024-03-29T13:51:27Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/611012018-09-05T08:56:28Zcom_10261_112com_10261_1col_10261_365
http://hdl.handle.net/10261/61101
10.1158/1541-7786.MCR-10-0515
63899
Long-Range Epigenetic Silencing Associates with Deregulation of Ikaros Targets in Colorectal Cancer Cells
American Association for Cancer Research
2011
artículo
Javierre, Biola M.
González-Sarmiento, Rogelio
rp08223
2011
Transcription factors are common targets of epigenetic inactivation in human cancer. Promoter hypermethylation and subsequent silencing of transcription factors can lead to further deregulation of their targets. In this study, we explored the potential epigenetic deregulation in cancer of Ikaros family genes, which code for essential transcription factors in cell differentiation and exhibit genetic defects in hematologic neoplasias. Unexpectedly, our analysis revealed that Ikaros undergoes very specific promoter hypermethylation in colorectal cancer, including in all the cell lines studied and around 64% of primary colorectal adenocarcinomas, with increasing proportions in advanced Duke's stages. Ikaros hypermethylation occurred in the context of a novel long-range epigenetic silencing (LRES) region. Reintroduction of Ikaros in colorectal cancer cells, ChIP-chip analysis, and validation in primary samples led us to identify a number of direct targets that are possibly related with colorectal cancer progression. Our results not only provide the first evidence that LRES can have functional specific effects in cancer but also identify several deregulated Ikaros targets that may contribute to progression in colorectal adenocarcinoma.
Molecular Cancer Research
2011
9
1139
1151