Details

Autor(en) / Beteiligte

• Exner, Ruth
• Pulverer, Walter
• Diem, Martina
• Spaller, Lisa
• Woltering, Laura
• Schreiber, Martin
• Wolf, Brigitte
• Sonntagbauer, Markus
• Schröder, Fabian
• Stift, Judith
• Wrba, Fritz
• Bergmann, Michael
• Weinhäusel, Andreas
• Egger, Gerda

Titel

Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers

Ist Teil von

• British journal of cancer, 2015-09, Vol.113 (7), p.1035-1045

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer.