By moving activating parts of the DNA into the vicinity of the cancer gene, the researchers show that mutations can turn on cancer genes, leading to uncontrolled cell growth. The new knowledge enables targeted therapy especially for patients with aggressive tumours as brain tumours, and may increase patient survival.
Cancer is caused by mutations in our DNA, which can be hereditable or occur spontaneously. Especially large changes in the DNA (called structural variants), where parts of the DNA is lost, copied or moved, is related to aggressive cancers. Most of these DNA changes occur in regions previously considered non-functional (non-coding regions), which was therefore called junk-DNA. However, recent research shows that these non-coding regions play a substantial role for our organism. This is further supported by the new results from the Weischenfeldt group at Finsen Laboratory, Rigshospitalet and BRIC, University of Copenhagen, obtained in collaboration with Jan Korbels group at EMBL and showing that changes in these regions can have serious consequences and result in increased cell proliferation.
- We have found that structural variants can change the DNA’s 3D structure. By moving cancer genes into the vicinity of active DNA parts called enhancers, the mutations turn on normally shut cancer genes. So by ’hijacking’ an active enhancer the cancer gene is activated, which can result in uncontrolled cancer cell growth, explains group leaders Joachim Weischenfeldt.
New knowledge combined with existing drugs
The genetic changes driving disease in many cancer patients is unknown, diminishing effective targeting of their tumour. The new results from the Weischenfeldt group can help find these genetic changes and thus gives hope for patients with aggressive cancers.
- We have found a new mechanism that can turn on cancer genes by connecting enhancer regions to normally inactive cancer genes. Drugs targeting such enhancers already exist, and can potentially be used to turn off a cancer gene again. The next step is to apply the results and tailor individual treatments of especially aggressive tumours, with the aim to increase patient survival, ends Joachim Weischenfeldt.
The results are published in the journal Nature Genetics and are partly supported by the Danish Council for Independent Research.