Background

We investigated the effects of chromosomal instability (CIN) on gene expression in colorectal adenoma to carcinoma progression, focusing on gain of chromosome 20 as this is one of the most prominent features of adenoma to carcinoma progression in CIN colorectal cancers. We have investigated two independent series of colorectal tumours, containing non-progressed adenomas, progressed adenomas and adenocarcinomas, and studied DNA copy number alterations by arrayCGH and mRNA expression by microarray analysis. Data analysis, focusing on putative oncogenes whose expression was correlated with DNA copy number ratio of the genomic region involved, was approached from multiple angles. Overlapping the results of these different approaches yielded a number of putative oncogenes involved in different biological pathways as being important effectors in CIN related adenoma to carcinoma progression.

Aim

Identify CIN-related genes involved in colorectal cancer progression

Plan of work

• In silico characterization of the candidate genes (structure, putative function, gene network)
• Make a construct where the target gene is under regulation of an actively transcribed gene
• Knock-in the target gene construct into colon cancer cell lines without chromosomal instability
• Analyse phenotypic changes in the cell lines (e.g. formation of micronuclei, mitotic spindle disfunction)
• Analyse by array-CGH the chromosomal aberrations in the cell lines before and after transfection of the target gene

Duration

6 months

More information

For more information please contact dr. R.J.A. Fijneman