| Title |
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer
|
|---|---|
| Published in |
Genome Biology, April 2015
|
| DOI | 10.1186/s13059-015-0605-5 |
| Pubmed ID | |
| Authors |
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 EK Ibrahim, François Fuks, Adele Murrell |
| Abstract |
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. 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. 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. |
X Demographics
The data shown below were collected from the profiles of 19 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 5 | 26% |
| United States | 5 | 26% |
| Spain | 1 | 5% |
| Venezuela, Bolivarian Republic of | 1 | 5% |
| Australia | 1 | 5% |
| Unknown | 6 | 32% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 9 | 47% |
| Scientists | 7 | 37% |
| Science communicators (journalists, bloggers, editors) | 2 | 11% |
| Practitioners (doctors, other healthcare professionals) | 1 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 140 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 1 | <1% |
| India | 1 | <1% |
| United Kingdom | 1 | <1% |
| Belgium | 1 | <1% |
| United States | 1 | <1% |
| Unknown | 135 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 35 | 25% |
| Researcher | 34 | 24% |
| Student > Master | 15 | 11% |
| Student > Doctoral Student | 11 | 8% |
| Other | 7 | 5% |
| Other | 22 | 16% |
| Unknown | 16 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 54 | 39% |
| Agricultural and Biological Sciences | 38 | 27% |
| Medicine and Dentistry | 8 | 6% |
| Chemistry | 4 | 3% |
| Computer Science | 3 | 2% |
| Other | 11 | 8% |
| Unknown | 22 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 April 2015.
All research outputs
#3,394,406
of 25,374,647 outputs
Outputs from Genome Biology
#2,417
of 4,467 outputs
Outputs of similar age
#42,373
of 279,170 outputs
Outputs of similar age from Genome Biology
#43
of 63 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,467 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 279,170 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.