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Open Access Highly Accessed Research article

Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

Ada Piepoli1*, Rosa Cotugno1, Giuseppe Merla2, Annamaria Gentile1, Bartolomeo Augello2, Michele Quitadamo1, Antonio Merla1, Anna Panza1, Massimo Carella2, Rosalia Maglietta3, Annarita D'Addabbo3, Nicola Ancona3, Saverio Fusilli4, Francesco Perri1 and Angelo Andriulli1

Author Affiliations

1 Gastroenterology Unit and Research Laboratory, "Casa Sollievo della Sofferenza", Hospital, IRCCS, San Giovanni Rotondo, Italy

2 Medical Genetics Service, "Casa Sollievo della Sofferenza", Hospital, IRCCS, San Giovanni Rotondo, Italy

3 Istituto di Studi sui Sistemi Intelligenti per l'Automazione – CNR, Bari, Italy

4 Health Services, "Casa Sollievo della Sofferenza", Hospital, IRCCS, San Giovanni Rotondo, Italy

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BMC Medical Genomics 2009, 2:11  doi:10.1186/1755-8794-2-11

Published: 3 March 2009



Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters.


The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC.


Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the

egulated gene 2 (NDRG2) promoter was found methylated in all CRC cell lines. NDRG2 hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated.


The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.