Research output: Contribution to journal › Article › peer-review
Santiago Uribe-Lewis, Rory Stark, Thomas Carroll, Mark J. Dunning, Martin Bachman, Yoko Ito, Lovorka Stojic, Silvia Halim, Sarah L. Vowler, Andy G. Lynch, Benjamin Delatte, Eric J. de Bony, Laurence Colin, Matthieu Defrance, Felix Krueger, Ana Luisa Silva, Rogier ten Hoopen, Ashraf E.K. Ibrahim, François Fuks, Adele Murrell
Background: The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise.
Results: Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells.
Conclusions: Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
Original language | English |
---|---|
Article number | 69 |
Number of pages | 15 |
Journal | Genome Biology |
Volume | 16 |
DOIs | |
Publication status | Published - 1 Apr 2015 |
Discover related content
Find related publications, people, projects and more using interactive charts.
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
ID: 250731008