A tiny bit less cancer

Medical biologist compares DNA in breast tumours

By Bart Braun

A Leiden doctoral candidate made of study of the genetics of breast cancer: "If two different tumours have a comparable genetic background, they could be treated in the same way."

The human body consists of thousands of billions of cells and we have huge range of tricks to prevent one of those turning into a cancer growth; nevertheless, it still happens, and depending on the exact type of cancer, things can go seriously wrong for you, even in 2012.

Other media sometimes feature articles like "Scientists discover cure for cancer" as if the right pill is just waiting to be found. This is not one of those articles. Back in 1972, American President Richard Nixon optimistically declared a "War on Cancer". The results so far: cancers stars prominently among the top ten of causes of death in wealthy countries. Of course, we are making progress, but only bit by bit.

Medical biologist Simon Joosse's dissertation, for which he was recently awarded his doctorate, is a small step in the right direction. It could help a tiny bit if you have a specific form of cancer – and that is actually quite significant in the reality of science. Not many Euros in the Dutch Cancer Society's collection boxes are used to the same immediate and rapid effect as the grant for his doctoral studies.

Because many kinds of cancer are partly genetically determined, scientists like Joosse are examining this genetic foundation in the hopes of learning something about how cancer develops or how it could be treated.

But first, here is a brief refresher course on genetics: hereditary information is stored as large DNA molecules, or chromosomes. This DNA consists of smaller molecules which biochemists have called A, T, C and G. Some pieces of a chromosome can be read by the cells; these are the genes. The specific purpose of some genes is to control other genes, while others create the building scheme for the protein molecules from which the body is constructed, and with which it does everything.

The genes Joosse was working on are called BRCA1 and BRCA2, or "Bracca" as the biologists say for short. Both these genes consist of many thousands of DNA letters, and if all those letters are correctly placed, the genes perform important work. Recently, it was discovered that BRCA1 has a part in the creation of milk glands in the breast, and both genes contain the building scheme for proteins that repair damaged DNA – a significant task, because damaged DNA can be the first step towards the development of cancer.

That is what happens in people where the letters are not correctly placed: most changes are not relevant to a gene, but when the changes have an effect, the owner of the mutant gene has a considerably higher risk of breast cancer. The genes owe their names to that fact: even before we knew their usual functions, the geneticists realised that the broken versions caused BReast CAncer.

Once you know that these genes exist and that damaged versions increase the risk of breast cancer, you can do something about it. You could study how your version of the genes is constructed. As this is still quite expensive, geneticists only examine women with a family history of breast cancer. And for the same reasons, they do not determine the exact order of all the As, Ts, Cs and Gs, but take short cuts.

Joosse's shortcut is called "Array Comparative Genomic Hybridization"; he did not use it to trace breast cancer patients, but to examine breast tumours. "It is a technique to compare two pieces of DNA," he explains. "Generally speaking, you have two versions of every chromosome, one inherited from your father and one from your mother. You label the control DNA green, and the tumour DNA red. The machine measures how much green and red there is. If you see more red, then you know that a piece of DNA occurs more often in the tumour than in healthy tissue. If you can see more green, then that bit of DNA is common in the cancer tissue, or else it's been eliminated."

Joosse discovered that the genetic composition – the amount of red and green – of tumours caused by a mutation in BRCA1 or BRCA2 differs from that of other breast tumours, which is useful to know. "There are families with many cases of breast cancer, but in whom no known BRCA-mutations were discovered. So now what do we do? Maybe we missed a mutation, because the genes are so large. But if you apply this technology to their tumours, you could discover new harmful versions of the gene and that would improve screening for other people.

"Perhaps someone has a non-BRCA-tumour that looks similar to BRCA tumour. Those people may have a mutation in a gene that we do not know of yet, but one that does something similar to the BRCA genes. But you could treat those patients in a similar fashion, by prescribing drugs that deal with the absence of DNA repair."

This has already tried with a small group of patients at the Netherlands Cancer Institute, where Joosse did his doctoral research. "They responded better to the treatment," says the doctoral candidate. But that doesn't mean to say they were all cured, he hastens to add: "We are still talking about surviving cancer for longer." But things are improving, bit by bit.

Simon Joosse, Prediction of "BRCAness"

in breast cancer by array comparative

genome hybridization

Deel dit bericht: