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5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer

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5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer. / Uribe-Lewis, Santiago; Stark, Rory; Carroll, Thomas; Dunning, Mark J.; Bachman, Martin; Ito, Yoko; Stojic, Lovorka; Halim, Silvia; Vowler, Sarah L.; Lynch, Andy G.; Delatte, Benjamin; de Bony, Eric J.; Colin, Laurence; Defrance, Matthieu; Krueger, Felix; Silva, Ana Luisa; ten Hoopen, Rogier; Ibrahim, Ashraf E.K.; Fuks, François; Murrell, Adele.

In: Genome Biology, Vol. 16, 69, 01.04.2015.

Research output: Contribution to journalArticle

Harvard

Uribe-Lewis, S, Stark, R, Carroll, T, Dunning, MJ, Bachman, M, Ito, Y, Stojic, L, Halim, S, Vowler, SL, Lynch, AG, Delatte, B, de Bony, EJ, Colin, L, Defrance, M, Krueger, F, Silva, AL, ten Hoopen, R, Ibrahim, AEK, Fuks, F & Murrell, A 2015, '5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer', Genome Biology, vol. 16, 69. https://doi.org/10.1186/s13059-015-0605-5

APA

Uribe-Lewis, S., Stark, R., Carroll, T., Dunning, M. J., Bachman, M., Ito, Y., ... Murrell, A. (2015). 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer. Genome Biology, 16, [69]. https://doi.org/10.1186/s13059-015-0605-5

Vancouver

Uribe-Lewis S, Stark R, Carroll T, Dunning MJ, Bachman M, Ito Y et al. 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer. Genome Biology. 2015 Apr 1;16. 69. https://doi.org/10.1186/s13059-015-0605-5

Author

Uribe-Lewis, Santiago ; Stark, Rory ; Carroll, Thomas ; Dunning, Mark J. ; Bachman, Martin ; Ito, Yoko ; Stojic, Lovorka ; Halim, Silvia ; Vowler, Sarah L. ; Lynch, Andy G. ; Delatte, Benjamin ; de Bony, Eric J. ; Colin, Laurence ; Defrance, Matthieu ; Krueger, Felix ; Silva, Ana Luisa ; ten Hoopen, Rogier ; Ibrahim, Ashraf E.K. ; Fuks, François ; Murrell, Adele. / 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer. In: Genome Biology. 2015 ; Vol. 16.

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@article{082f2f7cee284ea98292fa3b2c1704af,
title = "5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer",
abstract = "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.",
author = "Santiago Uribe-Lewis and Rory Stark and Thomas Carroll and Dunning, {Mark J.} and Martin Bachman and Yoko Ito and Lovorka Stojic and Silvia Halim and Vowler, {Sarah L.} and Lynch, {Andy G.} and Benjamin Delatte and {de Bony}, {Eric J.} and Laurence Colin and Matthieu Defrance and Felix Krueger and Silva, {Ana Luisa} and {ten Hoopen}, Rogier and Ibrahim, {Ashraf E.K.} and Fran{\cc}ois Fuks and Adele Murrell",
note = "The authors would like to acknowledge the support of The University of Cambridge, Cancer Research UK (CRUK SEB-Institute Group Award A ref10182; CRUK Senior fellowship C10112/A11388 to AEKI) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FF is a ULB Professor funded by grants from the F.N.R.S. and T{\'e}l{\'e}vie, the IUAP P7/03 programme, the ARC (AUWB-2010-2015 ULB-No 7), the WB Health program and the Fonds Gaston Ithier. Data access: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jpwzvsowiyuamzs&acc=GSE47592",
year = "2015",
month = "4",
day = "1",
doi = "10.1186/s13059-015-0605-5",
language = "English",
volume = "16",
journal = "Genome Biology",
issn = "1465-6906",
publisher = "BioMed Central",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer

AU - Uribe-Lewis, Santiago

AU - Stark, Rory

AU - Carroll, Thomas

AU - Dunning, Mark J.

AU - Bachman, Martin

AU - Ito, Yoko

AU - Stojic, Lovorka

AU - Halim, Silvia

AU - Vowler, Sarah L.

AU - Lynch, Andy G.

AU - Delatte, Benjamin

AU - de Bony, Eric J.

AU - Colin, Laurence

AU - Defrance, Matthieu

AU - Krueger, Felix

AU - Silva, Ana Luisa

AU - ten Hoopen, Rogier

AU - Ibrahim, Ashraf E.K.

AU - Fuks, François

AU - Murrell, Adele

N1 - The authors would like to acknowledge the support of The University of Cambridge, Cancer Research UK (CRUK SEB-Institute Group Award A ref10182; CRUK Senior fellowship C10112/A11388 to AEKI) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FF is a ULB Professor funded by grants from the F.N.R.S. and Télévie, the IUAP P7/03 programme, the ARC (AUWB-2010-2015 ULB-No 7), the WB Health program and the Fonds Gaston Ithier. Data access: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jpwzvsowiyuamzs&acc=GSE47592

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

U2 - 10.1186/s13059-015-0605-5

DO - 10.1186/s13059-015-0605-5

M3 - Article

VL - 16

JO - Genome Biology

JF - Genome Biology

SN - 1465-6906

M1 - 69

ER -

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