Lack of gene expression associated with ovarian cancer

The expression of two specific genes is almost completely downregulated in ovarian cancer tumours. An extensive analysis of gene expression in ovarian cancer tumour cells has revealed this important finding, which should be an aid to early diagnosis. The insights gained by the research at the Medical University of Vienna with the support of the Austrian Science Fund FWF are also central to a recently launched EU project aimed at optimising ovarian cancer diagnosis.

Model of the expression of five genes in 58 tumour samples. Blue indicates below-average and red above-average expression. © Use of this photo for editorial purposes is free of charge, subject to attribution: Michael Krainer

Some 63,000 cases of ovarian cancer are diagnosed in Europe every year. The systems of the disease seldom appear until it has reached an advanced stage, by which time it is often too late for effective treatment. Delayed diagnosis causes over 30,000 deaths.

In the genes
A team led by Prof. Michael Krainer of the Clinic for Internal Medicine I at the Medical University of Vienna that has been looking for an early diagnosis method has now made a major breakthrough. Comparison of normal ovarian cells with advanced ovarian cancer cells highlighted molecular genetic differences. The genes identified as N33 and EFA6R are in some cases almost completely inactivated in the cancer cells. Commenting on the usefulness of the discovery in the diagnosis of cancer, Prof. Krainer noted: "At present it looks as though these two genes have already lost their activity before the appearance of clinical symptoms. We presume that this happens because methyl groups are attached to the gene's building blocks. This is a common means of regulating gene activity. Methylation like this is easy to detect and could be an early warning sign for a developing cancer."

The expression of several genes on a particular band of the human chromosome 8 in tumour cells from over 90 patients were measured during the FWF project. In ovarian cancer there is often a loss of this chromosomal band. Earlier work in this area by Prof. Krainer's team had already identified 22 genes. The current project has now been able to demonstrate that a total of five of these genes show very low expression levels in tumour cells. N33 and EFA6R stood out, as the reduction in their expression was associated with the progression of the disease. However, as yet the function of the genes can only be speculated on. N33 may be involved in the regulation of cell death and EFA6R in signal transmission.

Coming to your screens
Together with Prof. Robert Zeillinger's group at the Gynaecology and Obstetrics Clinic, Prof. Krainer has succeeded in establishing a core research focus on molecular cancer diagnostics that has gained an international reputation. Only a short time ago the Austrian scientists succeeded in identifying a receptor molecule, the absence of which promotes the development of ovarian cancer, and now they are also coordinating groups in six countries in an EU project that has just been approved. The aim of the EUR 4 million project is to identify molecular markers that would permit early diagnosis of ovarian cancer.

Highlighting the advances being made in cancer diagnosis, Prof. Krainer said: "The next step in early detection is the diagnosis of molecular genetic markers such as methylations, as they provide information on the actual development of cancer in individual patients. This means that analysis of molecular genetic markers is an ideal match for diagnosis of genetic predisposition to breast and colon cancers, for example." The diagnosis of genetic predispositions offers vital information on the likelihood that a person will have a hereditary disposition for these types of cancer. Today these genetic diagnostics already offer opportunities for adjusting expensive screening tests to individual risk profiles. This saves lifes and money - the reason why Dutch health insurance funds are prepared to pay for genetic diagnosis.

Original publication: Five genes from chromosomal band 8p22 are significantly downregulated in ovarian cancer: N33 und EFA6R have a potential impact on overall survival. Cancer 15.11.2005 Advanced On-line Publication

Scientific contact
Prof. Michael Krainer
Medical University of Vienna
Austria
T +43 / 664 / 183 76 77
michael.krainer(at)meduniwien.ac.at

Austrian Science Fund FWF
Mag. Stefan Bernhardt

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