A tissue-based comparative effectiveness analysis of biomarkers for early detection of colorectal tumors.

Objectives: We recently identified a six-gene methylation-based biomarker panel suitable for early detection of colorectal cancer (CRC). In this study, we compared the performance of this novel epi-panel with that of previously identified DNA methylation markers in the same clinical tissue sample sets.

Methods: Quantitative methylation-specific PCR was used to analyze the promoter region of SEPT9 and VIM in a total of 485 tissue samples, divided into test and validation sets.

Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation.

In sarcomas, the TP53 tumour suppressor pathway may be altered either by TP53 mutations or by amplification of MDM2, encoding a protein that inhibits TP53 and targets it for 26S-proteasome degradation. However, in the majority of the analysed clinical samples, neither of these types of aberrations are found, suggesting that additional mechanisms are involved. The present study shows that COPS3, located in 17p11 and encoding a component of the proteasome pathway, is more frequently amplified in osteosarcomas (OS) than is MDM2.

WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability.

Background & Aims: Microsatellite instability (MSI) is the phenotype of colorectal carcinomas with defect mismatch repair. Genes with repetitive sequences within their coding regions are targets for mutations in these tumors. We have evaluated 2 novel candidate genes for potential involvement in development of MSI colorectal carcinomas and compared them with alterations in known target genes.