Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression

Ashraf E K Ibrahim, Mark J Arends, Ana-Luisa Silva, Andrew H Wyllie, Liliana Greger, Yoko Ito, Sarah L Vowler, Tim H-M Huang, Simon Tavaré, Adele Murrell, James D Brenton

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Although aberrant methylation of key genes in the progression of colorectal neoplasia has been reported, no model-based analysis of the incremental changes through the intermediate adenoma stage has been described. In addition, the biological drivers for these methylation changes have yet to be defined. Linear mixed-effects modelling was used in this study to understand the onset and patterns of the methylation changes of SFRP2, IGF2 DMR0, H19, LINE-1 and a CpG island methylator phenotype (CIMP) marker panel, and they were correlated with DNA methyltransferase 3B (DNMT3B) levels of expression in a sample set representative of colorectal neoplastic progression.
Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalGut
Volume60
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Adenocarcinoma
  • Adenoma
  • Aged
  • Aged, 80 and over
  • Colon
  • Colonic Polyps
  • Colorectal Neoplasms
  • CpG Islands
  • DNA (Cytosine-5-)-Methyltransferase
  • DNA Methylation
  • DNA, Neoplasm
  • Disease Progression
  • Female
  • Humans
  • Hyperplasia
  • Insulin-Like Growth Factor II
  • Liver Neoplasms
  • Male
  • Membrane Proteins
  • Microsatellite Repeats
  • Middle Aged
  • Precancerous Conditions
  • Tumor Markers, Biological

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  • Cite this

    Ibrahim, A. E. K., Arends, M. J., Silva, A-L., Wyllie, A. H., Greger, L., Ito, Y., Vowler, S. L., Huang, T. H-M., Tavaré, S., Murrell, A., & Brenton, J. D. (2011). Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression. Gut, 60(4), 499-508. https://doi.org/10.1136/gut.2010.223602