DNA fingerprinting helps to heal brain cancer

Disease and treatment 8. may 2018 2 min Klinisk professor, Professor Bjarne Winter Kristensen Written by Morten Busch

At least 100 types of tumours can strike the brain and central nervous system. Some need to be treated immediately. Others are benign, and chemotherapy may therefore be harmful. Until now, the diagnostic process has relied on imprecise microscopic samples, but researchers have discovered a unique DNA fingerprint for each type of tumour through a new method described in an article in Nature. As a result, 10% of patients can get better treatment, have an increased chance of surviving and avoid the side-effects of unnecessary treatment.

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How important are our genes and how important is the environment? Humans have asked themselves this question for centuries. Tiny chemical molecules play an important role in the interaction between genes and the environment by embedding themselves in our genes and helping to control which genes are expressed and which ones are silenced. Stress and old age can influence the changes. An international research group with Danish participation has revealed that the pattern of genetic changes can be used to differentiate types of tumours in the central nervous system.

“Using this method enables us to draw a much more precise picture of the individual tumour than the process today, in which an individual type of tumour is determined thorough magnetic resonance imaging, microscopy and sequencing selected genes. Our study showed that at least 10% of patients currently receive incorrect treatment or follow-up because they are thought to have another type of tumour than the one they actually have. By examining the pattern of chemical changes in the tumour’s DNA, we can determine very precisely the type of tumour and thereby initiate appropriate treatment immediately,” explains Bjarne W. Kristensen, Professor of Pathology, University of Southern Denmark.

850,000 possible changes

The tiny chemical changes on the surface of DNA the researchers measure are called epigenetic markers. If a methyl group, for example, embeds itself in a specific gene, this can suppress the transcription of the gene. Thus, the chemical modifications regulate activity in a specific cell. Tumours have abnormal activity and therefore often a different profile of chemical changes to the surface of the DNA.

This new method enables us to create a kind of DNA fingerprint showing where the chemical modifications are. We have access to a library of 3000 tumours, so we can now classify 82 types of tumours very accurately based on the chemical changes of their DNA.

This is no mean task the researchers have undertaken: measuring about 850,000 possible sites in genes with or without a methyl group. Although this is a very precise tool, the work is very time-consuming, requiring several days of work by bioanalysts followed by collaboration between molecular biologists and pathologists. However, the results the Danish researchers obtained with this method were amazing.

The primary diagnosis is still based on microscopic analysis, but if there is the slightest doubt about the type of tumour, we analyse a sample before starting treatment. Because providing correct treatment from the start for people with cancer is absolutely vital, we can help doctors confirm the correct treatment if they are in any doubt about the type of tumour.

Useful for other types of cancer

A major international collaboration between molecular biologists, bioinformaticians and pathologists developed the new method. In Denmark, the research was carried out at the University of Southern Denmark and Odense University Hospital. Samples from this Hospital and from others in Denmark and Scandinavia were analysed in situations in which the results of analysis of brain tumours were unclear.

We analyse about 100 samples annually. Of these, up to one fifth of the diagnoses change, and this is very significant for these patients. Many had a more serious initial diagnosis than their actual situation, so they could avoid treatment that was potentially disabling. Although the new diagnosis was worse for some, treatment could start immediately, drastically increasing their chances of surviving longer.

Rigshospitalet in Copenhagen has also introduced this method, and research on developing and using the method continues in Scandinavia. The hope is that adding several rare tumours to the library can make the method even more nuanced.

When we get more data, we will be able to see even more subgroups of fingerprints that we hope will enable us to identify more subgroups of brain tumours that each have an ideal type of treatment. We also believe that this method should be able to be used on other types of cancer, leading to improved diagnosis and treatment of these other problematic types.

DNA methylation-based classification of central nervous system tumours” has been published in Nature. The Novo Nordisk Foundation awarded a grant in 2012 to Bjarne W. Kristensen, University of Southern Denmark for the project Test of Specific Drug in Preclinical Models of Glioblastoma.

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