New findings show hereditary defect causes certain brain tumours

New findings show hereditary defect causes certain brain tumours

Certain dangerous brain tumours – called medulloblastoma – that affect children are caused by a hereditary genetic defect.

According to new research published in the journal Nature, the causes of 40% of all cases of certain medulloblastoma – dangerous brain tumours affecting children – are from a hereditary defect. The findings come from a recent genetic analysis carried out by scientists from the Hopp Children’s Cancer Center (KiTZ), the European Molecular Biology Laboratory (EMBL) and numerous colleagues around the world.

The findings show that a genetic defect that occurs in 15% children with these tumours plays a key role by destabilising the production and breakdown of proteins. The researchers suspect that protein metabolism defects could be a previously underestimated cause of other types of cancer.

Medulloblastoma tumours

Medulloblastoma are among the most common malignant brain tumours affecting children. They spread from the cerebellum to the surrounding tissue and can also spread to other parts of the central nervous system via the cerebrospinal fluid. Because these tumours grow rapidly, physicians do not have much time to find a suitable treatment.

The researchers conducted the most comprehensive medulloblastoma-related genetic investigation to date – analysing the genome and tumour genome of 800 children, young people and adults with medulloblastoma. This analysis was then compared the genetic data with data from healthy individuals, finding a hereditary difference in children and young people with brain tumours in the ‘Sonic Hedgehog’ medulloblastoma subgroup.

The hereditary genetic defect meant that patients were no longer able to produce the elongator complex protein 1 (ELP1) in the tumour.

The latest findings show that, without ELP1, much of the protein metabolism is disturbed.

KiTZ Director Stefan Pfister, who is a head of department at the DKFZ and an expert in targeted therapies within the DKTK, said: “The assembly and folding of larger proteins in particular does not function properly any more, and the accumulation of these non-functioning or malfunctioning proteins places the cells under permanent stress.

“Hundreds of proteins are misregulated in this way, including proteins that are important for nerve cell development.”

Through the analysis of the genome of some parents and grandparents, the researchers also established that the cancer activating ELP1 genetic defect is hereditary.

“That makes this the most common congenital genetic defect associated with medulloblastoma to date”, says Jan Korbel, a co-author of the study who works at EMBL.

Identifying hereditary causes of cancer in advance can help to make the right therapeutic decision and reduce the risk of relapse in children.

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