Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

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Updated: Jun 25, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

Ada Piepoli1, Rosa Cotugno, Giuseppe Merla

  • 1Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy. a.piepoli@operapadrepio.it

BMC Medical Genomics
|March 5, 2009
PubMed
Abstract

Insights

Aberrant DNA methylation in colorectal cancer (CRC) genes is common. This study validates NDRG2 hypermethylation in CRC tissues, linking it to advanced stage and suggesting its role in tumor invasiveness.

Area of Science:

  • Molecular Oncology
  • Epigenetics
  • Cancer Biomarkers

Background:

  • Aberrant DNA methylation of CpG islands is an early event in cancerogenesis.
  • This epigenetic alteration frequently inactivates tumor-suppressor genes.
  • Identifying novel hypermethylated genes can aid cancer diagnosis and recurrence evaluation.

Purpose of the Study:

  • To validate previous microarray findings on cancer-related genes.
  • To identify novel hypermethylated gene promoters in colorectal cancer (CRC).

Main Methods:

  • Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) for validation in 8 CRC patients.
  • Comparison of RNA expression profiles in CRC cell lines before and after 5-aza-2'-deoxycytidine treatment.
  • Bisulphite genomic sequencing and methylation-specific PCR (MSP) to assess DNA methylation in cell lines and 30 CRC tumor tissues.

Main Results:

  • Six genes showed high induction post-treatment in CRC cell lines, confirming prior data.
  • NDRG2 (N-myc downstream-regulated gene 2) promoter was methylated in all CRC cell lines.
  • NDRG2 hypermethylation detected in 27% of primary CRC tissues, associated with advanced AJCC stage IV; normal tissues were unmethylated.

Conclusions:

  • Combining gene expression and epigenetic data is valuable for identifying tumor biomarkers.
  • NDRG2 silencing may influence tumor invasiveness and is linked to advanced CRC stage.
  • NDRG2 hypermethylation shows potential as a diagnostic or prognostic biomarker in colorectal cancer.

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