Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticlepeer-review

Author(s)

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

School/Research organisations

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.

Close

Details

Original languageEnglish
Article number69
Number of pages15
JournalGenome Biology
Volume16
DOIs
Publication statusPublished - 1 Apr 2015

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. CamGFR v2: a new model for estimating the glomerular filtration rate from standardized or non-standardized creatinine in patients with cancer

    Williams, E. H., Flint, T. R., Connell, C. M., Giglio, D., Lee, H., Ha, T., Gablenz, E., Bird, N. J., Weaver, J. M. J., Potts, H., Whitley, C. T., Bookman, M. A., Lynch, A. G., Meyer, H. V., Tavaré, S. & Janowitz, T., 12 Jan 2021, In: Clinical Cancer Research. Online First

    Research output: Contribution to journalArticlepeer-review

  2. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

    PCAWG Consortium, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Bailey, M. H., Meyerson, W. U., Dursi, L. J., Wang, L-B., Dong, G., Liang, W-W., Weerasinghe, A., Li, S., Li, Y., Kelso, S., Saksena, G., Ellrott, K., Wendl, M. C., Wheeler, D. A., Getz, G., Simpson, J. T., Gerstein, M. B. & 2 others, Ding, L. & Lynch, A., 21 Sep 2020, In: Nature Communications. 11, 27 p., 4748 .

    Research output: Contribution to journalArticlepeer-review

  3. Sex differences in oncogenic mutational processes

    Li, C. H., Prokopec, S. D., Sun, R. X., Yousif, F., Schmitz, N., PCAWG Tumour Subtypes and Clinical Translation, Boutros, P. C., PCAWG Consortium & Lynch, A., 28 Aug 2020, In: Nature Communications. 11, 24 p., 4330 .

    Research output: Contribution to journalArticlepeer-review

  4. Whole-genome sequencing of a sporadic primary immunodeficiency cohort

    Primary Immunodeficiency Consortium for the NIHR Bioresource & Lynch, A. G., 6 May 2020, In: Nature.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Wnt evolution and function shuffling in liberal and conservative chordate genomes

    Somorjai, I. M. L., Marti-Solans, J., Diaz-Gracia, M., Nishida, H., Imai, K., Escriva, H., Cañestro, C. & Albalat, R., 25 Jul 2018, In: Genome Biology. 19, 17 p., 98.

    Research output: Contribution to journalArticlepeer-review

  2. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice

    Harkins, C. P., Pichon, B., Doumith, M., Parkhill, J., Westh, H., Tomasz, A., de Lencastre, H., Bentley, S. D., Kearns, A. M. & Holden, M. T. G., 20 Jul 2017, In: Genome Biology. 18, 11 p., 130.

    Research output: Contribution to journalArticlepeer-review

  3. The genome of the yellow potato cyst nematode, Globodera rostochiensis, reveals insights into the basis of parasitism and virulence

    Eves-van den Akker, S., Laetsch, D. R., Thorpe, P., Lilley, C. J., Danchin, E. G. J., Da Rocha, M., Rancurel, C., Holroyd, N. E., Cotton, J. A., Szitenberg, A., Grenier, E., Montarry, J., Mimee, B., Duceppe, M-O., Boyes, I., Marvin, J. M. C., Jones, L. M., Yusup, H. B., Lafond-Lapalme, J., Esquibet, M. & 14 others, Sabeh, M., Rott, M., Overmars, H., Finkers-Tomczak, A., Smant, G., Koutsovoulos, G., Blok, V., Mantelin, S., Cock, P. J. A., Phillips, W., Henrissat, B., Urwin, P. E., Blaxter, M. & Jones, J. T., 10 Jun 2016, In: Genome Biology. 17, 23 p., 124.

    Research output: Contribution to journalArticlepeer-review

  4. Evolutionary dynamics of methicillin-resistant Staphylococcus aureus within a healthcare system

    Hsu, L-Y., Harris, S. R., Chlebowicz, M. A., Lindsay, J. A., Koh, T-H., Krishnan, P., Tan, T-Y., Hon, P-Y., Grubb, W. B., Bentley, S. D., Parkhill, J., Peacock, S. J. & Holden, M. T. G., 23 Apr 2015, In: Genome Biology. 16, 13 p., 81.

    Research output: Contribution to journalArticlepeer-review

ID: 250731008

Top