4.6 Article

Array-based identification of common DNA methylation alterations in ulcerative colitis

Journal

INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 40, Issue 4, Pages 983-994

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2011.1283

Keywords

ulcerative colitis associated carcinogenesis; methylation profiling; field cancerization; methylation sensitive amplified fragment length polymorphism; microarray; MS-AFLP

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Funding

  1. Jichi Medical University
  2. Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain [PI09/02444]
  3. ICREA Funding Source: Custom

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Patients with long-standing ulcerative colitis (UC) have higher risk of developing colorectal cancer. Albeit the causes remain to be understood, epigenetic alterations have been suggested to play a role in the long-term cancer risk of these patients. In this work, we developed a novel microarray platform based on methylation-sensitive amplified fragment length polymorphism (MS-AFLP) DNA fingerprinting. The over 10,000 NotI sites of the human genome were used to generate synthetic primers covering these loci that are equally distributed into CpG rich regions (promoters and CpG islands) and outside the CpG islands, providing a panoramic view of the methylation alterations in the genome. The arrays were first tested using the colon cancer cell line CW-2 showing the reproducibility and sensitivity of the approach. We next investigated DNA methylation alterations in the colonic mucosa of 14 UC patients. We identified epigenetic alterations affecting genes putatively involved in UC disease, and in susceptibility to develop colorectal cancer. There was a strong concordance of methylation alterations (both hypermethylation and hypomethylation) shared by the cancer cells of the CW-2 cell line and the non-cancer UC samples. To the best of our knowledge, this work defines the first high-throughput aberrant DNA methylation profiles of the colonic mucosa of UC patients. These epigenetic profiles provide novel and relevant knowledge on the molecular alterations associated to the UC pathology. Some of the detected alterations could be exploited as cancer risk predictors underlying a field defect for cancerization in UC-associated carcinogenesis.

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