Candidate genes found which may play a role in cancer progressing from non-invasive to invasive

Scientists in America have made the first steps in identifying a group of genes which may be involved in the progression of breast cancer from non-invasive to invasive, the 3rd European Breast Cancer Conference in Barcelona heard today (Thursday 21 March).

Professor Craig Allred, Director of Breast Pathology at the Breast Center, Baylor College of Medicine, Houston, USA, used a technique called microarray to discover which genes might be involved in causing ductal carcinoma in situ (DCIS) to progress to invasive breast cancer (IBC). Microarray studies involve using a microchip bearing thousands of known single-stranded gene fragments on its surface and incubating it with RNA from tissue samples. By seeing which gene fragments the RNA is attracted to it is possible to tell which genes are active in the tissue samples.

Prof Allred said: “DCIS is very common and gives rise to most IBCs. We already know that DCIS contains many genetic defects that are responsible for its development in the first place, but we believe that there are many additional genetic defects that must occur in DCIS to cause it to progress to IBC. Identifying the important genes will be useful because finding defects in them could help doctors to predict the outcome for the patients and, more importantly, could give us targets at which we could aim treatments to prevent or suppress invasion.”

Analyses of the results from the microarray studies showed that there were at least 100 individual genes which had significantly different levels of activity in DCIS and IBC, and many of these genes are known already to involve processes and pathways which could make them reasonable candidates as invasion-related genes.

Prof Allred said: “I don’t know whether any of the genes are truly ‘invasion-related’, but many of them are involved in biological pathways that are likely to be important in invasion. For example, several integrin genes, which are involved in making cells stick together, appear to be switched off in invasive tumours compared to non-invasive tumours. It is reasonable to assume from this that defects in these genes might make cells less sticky, which is probably necessary to becoming invasive. There are probably many defects involving processes such as cell adhesion, cell motility and so on that are required to make a normal breast cell become a malignant invasive cell. I expect these defects are acquired individually and accumulate over many years”

He continued: “The microarray experiments are only the first step to identifying candidate genes which may be important in invasion. Now we have to carry out further studies to discover whether they really are important or not. This will involve looking more closely at the proteins encoded by the genes, using clinical follow-up to see whether the genetic defects seen in the tumours are related to the outcome for the patient so that we know whether they are prognostic, and then testing whether the genes are actually responsible for suppressing or promoting tumour invasion.

“A few other laboratories are looking at this problem using different technical approaches and even with this group effort we are at least a few years away from actually having something to translate directly to patient care. If we do find genes responsible for tumour invasion, and if we can develop treatments to correct or prevent defects in them, then we have the chance to prevent lethal invasive breast cancer.”