 The team have used microarray and quantitative PCR methods to compare gene expression patterns between colorectal tissue obtained from normal patients with no evidence of colon cancer and the “normal” tissue adjacent to colorectal cancers. This has allowed identification of numerous genes whose expression is differentially regulated between the two patient groups (see image on left). This figure shows how many genes are expressed more highly in adjacent normal tissue (red), whereas others are expressed at lower levels (blue). The different patterns between the two tissues are obvious. Significantly, the normal tissue from the 20 normal patients without colon cancer show a similar expression signature, which indicates that this expression pattern is important for a completely normal phenotype.
Importantly, it has also been shown that the altered expression pattern is not influenced by the tumour, a so-called “field effect”, but is present at sites distal to the tumour (Centre Figure). This figure compares the expression levels of several genes at sites adjacent to and more distal to the cancer. If there was a field effect, the expression levels would be expected to be different (either up or down) closer to the tumour. 
Clearly, this is not the case. This is critical, as it suggests that the normal colon from patients with colorectal cancers is characterised by an expression profile that is different from that of a truly normal colon. Importantly, this raises the possibility that a subset of these differentially expressed genes could be used to predict cancer risk in normal, asymptomatic individuals.
Indeed, the team have identified a subset of markers that constitute a “diagnostic index” (Bottom Figure). This is made up from six genes that are differentially expressed between normal and adjacent normal tissue and it is apparent that there is a cut-off point: all adjacent normal tissue samples fall below this point, whereas most of the normal tissue samples fall above that point. The expectation is that those samples from normal tissue that fall below the cut-off point are indicative of increased cancer risk.
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