Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 N-myc downstream-regulated gene 2 (<it>NDRG2) </it>promoter was found methylated in all CRC cell lines. <it>NDRG2 </it>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.</p> <p>Conclusion</p> <p>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.</p

Inaccuracy of dipyridamole echocardiography or scintigraphy for the diagnosis of coronary artery disease in patients with both left bundle branch block and left ventricular dysfunction

Non-invasive diagnosis of coronary artery disease (CAD) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains challenging, and there is no consensus on the role of myocardial sesta-MIBI perfusion scintigraphy with pharmacological stress (dip-MIBI) or dipiridamole echocardiography (dip-ECHO). We thus performed a prospective study to test the diagnostic accuracy of such non-invasive tests. 27 consecutive patients with both LV dysfunction and LBBB undergoing diagnostic work-up for CAD were studied simultaneously with dip-ECHO and dip-MIBI. The sensitivity for CAD for dip-ECHO and dip-MIBI was respectively 42% and 67%, with specificity 93% and 53%, and likelihood ratio (LR)-positive 6.3 and LR-negative 0.6 for both. Given the low accuracy of both dip-ECHO and dip-MIBI in detecting CAD in patients with concomitant LV dysfunction and LBBB, coronary angiography should be performed as the default diagnostic strategy in such patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved