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Breast cancer gene

Friday 31 August 2007

The gene known as Tip60 has been linked to breast cancer, reported BBC News on 29 August 2007. Tip60 was shown not to work as well in breast cancer tissue as in normal tissue, and “low Tip60 activity was particularly associated with aggressive tumours”, it reported. It said that researchers suggest the finding has implications for treatment of breast cancer, and low Tip60 levels could be used as an indicator of aggressive tumours, leading to appropriate treatment being given.

This news report is based on a study in mice, and on human tumour tissue. Although the study seems reliable, the results should be considered preliminary. It is not yet known if Tip60 will have a role in directing cancer treatment.

Where did the story come from?

Chiara Gorrini and colleagues from universities and research institutes in Italy, the UK, Canada, and the USA carried out this research. The study was funded by the Italian Association for Cancer Research, the Italian Health Ministry, the National Institutes for Health in the USA, the National Cancer Institute of Canada, and the CancerCare Manitoba Foundation and was published in the peer-reviewed scientific journal: Nature.

What kind of scientific study was this?

There were two parts to this study. The first part was an animal study which aimed to look at the function of the Tip60 gene. Tip60 is thought to be a tumour suppressor gene, which means that it stops cells multiplying in an uncontrolled way. If tumour suppressor genes stop working, then cells may be able to divide rapidly, and a tumour may form. Researchers removed one copy of the Tip60 gene  from laboratory mice (a normal mouse would have two copies of the gene). They then looked at the effect this had on how fast the mice developed cancer of the white blood cells (lymphoma), and at various complex biochemical reactions in the cells.

The second part of the study was a pathological and genetic study, where the researchers looked at the Tip60 gene and protein in both normal and cancerous human tissue. The researchers took small samples of tissue from human head and neck cancers, breast cancers, and lymphomas and also normal tissue from these areas in the same individuals. They then compared how active the Tip60 gene was in these tissues. When the Tip60 gene is active it produces TIP60 protein; the researchers measured how much TIP60 protein there was in 10 different tumour types, including breast, lung, stomach, and colon compared with normal tissue from the same individuals.

What were the results of the study?

In the first part of the study, researchers found that the removal of one copy of theTip60 gene from the cancer-prone mice caused the mice to develop lymphomas faster. In the second part of the study, the researchers found that the gene was less active in some (but not all) breast cancers than in normal tissue, particularly in the more aggressive cancers. In some cases, the reduced activity was associated with the loss of one copy of the gene. The researchers also found that there appeared to be less TIP60 protein in some breast cancers than in normal breast tissue. Once again, this was particularly common in the more aggressive tumours. The researchers found similar results in some other types of cancers.

What interpretations did the researchers draw from these results?

The researchers concluded that in mice and humans, Tip60 acts as a tumour suppressor, and its function can be affected by loss of a single copy of the gene.

What does the NHS Knowledge Service make of this study?

This was a very complex study. It does show that Tip60 may play a role in the development of various tumours, including breast cancer. However, it looked only at a relatively small number of breast tumours (about 250 samples), and therefore the results should be replicated in a larger numbers of samples to confirm these results. In the newspaper reports, the researchers suggest that this discovery may have implications for the treatment of breast cancer, possibly in the identification of women with particularly aggressive tumours. However, more research is needed to investigate whether Tip60 is a good indicator of how aggressive a tumour is, and whether it adds anything to current diagnosis methods. Researchers also need to investigate how tumours with low levels of Tip60 respond to treatment. Further research is also needed into what Tip60 does in the cell and how it interacts with the other genes that are known to play a role in breast cancer.

Sir Muir Gray adds...

It is now clear that instead of talking about breast cancer or prostate cancer to describe the disease, we should be talking about breast cancers or prostate cancers, as even when two cancers look the same under the microscope they may behave very differently. This phenomenon is called "tigers and pussy cats" by some pathologists: two cancers can look just the same when a little bit comes into focus but behave very differently; some grow slowly, others spread very quickly.

The difference in the agressiveness of the cancers lies in the genetics and studies like this will help us identify people who need intensive treatment and those who need minimal treatment, or no treatment at all. For example, most men with prostate cancer will die of some other cause, whether they have treatment or not.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Faulty gene linked to breast cancer.

BBC News, 29 August 2007

Links to the science

Gorrini C, Squatrito M, Luise C, et al.

Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response.

Nature 2007; 448:1063-1067