Defective DNA Repair Leads to Genome “Chaos”
Scientists have found a cause for the frequent and damaging events in cancer cells’ genetic material where sections of individual chromosomes are broken at a number of points and reassembled wrongly, so entire sections are missing and others duplicated or incorporated in a wrong orientation.
This “chaos” in the genome, originally discovered several years ago by scientists from the German Cancer Research Center (DKFZ) and others and identified initially in an aggressive type of childhood brain tumour, differed from all previously-known genetic defects in tumours.
Such chromosomal destruction, known as “chromothripsis”, occurs in around 20-30% of all cancers. Now, scientists from DKFZ have found that this process stems from the failure of certain genetic repair systems.
The scientists switched off the DNA repair systems in the neural precursor cells of mice, which then developed malignant brain tumours which exhibited chromothripsis at a high frequency. This is nearly always accompanied by extra copies of the Myc oncogene, which is known to be a strong driver of cell growth.
This connection also applies to human brain tumours, melanomas and breast cancers, the team has confirmed.
One of the DKFZ researchers noted that the development of substances to block central DNA repair systems could combat this process: “If the analysis of a patient’s tumour genome reveals evidence of chromothripsis, treatment with PARP inhibitors could be a new therapeutic option in the future.
“Of course, this has to be confirmed in pre-clinical and clinical tests.”