Medulloblastoma

New insights into deadly brain tumours in children

The causes of 40 percent of all cases of certain medulloblastoma – dangerous brain tumors affecting children – are hereditary.

These are the findings of 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, which have just been published in the scientific journal Nature. A genetic defect that occurs in 15 percent of these children plays a key role by destabilizing the production and breakdown of proteins. The researchers suspect that protein metabolism defects could be a previously underestimated cause of other types of cancer.

Photo
Without the ELP1 assembly and folding of proteins does not function properly any more

© A. Moosmann

Medulloblastoma are among the most common malignant brain tumors 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 tumors grow rapidly, physicians do not have much time to find a suitable treatment.

Physicians at the Hopp Children's Cancer Center (KiTZ) specialize in characterizing the molecular properties of children's cancers in order to be able to recommend other treatment options besides standard therapies, and to develop new therapies with a focus on the mode of action. Together with colleagues from EMBL, the German Cancer Consortium (DKTK) and the St. Jude Children's Research Hospital in Memphis, USA, the KiTZ researchers conducted the most comprehensive medulloblastoma-related genetic investigation to date. They analyzed the genome and tumor genome of 800 children, young people and adults with medulloblastoma and compared the genetic data with data from healthy individuals. In doing so, they came across a particularly striking hereditary difference in children and young people with brain tumors in the Sonic Hedgehog medulloblastoma subgroup.

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

Stefan Pfister

A hereditary genetic defect in 15 percent of cases meant that patients were no longer able to produce the elongator complex protein 1 (ELP1) in the tumor. The elongator complex protein is involved in ensuring that proteins are properly assembled and folded in line with the genetic code. The latest findings show that, without ELP1, much of the protein metabolism is disturbed: "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," says KiTZ Director Stefan Pfister, who is a head of department at the DKFZ and an expert in targeted therapies within the DKTK. "Hundreds of proteins are misregulated in this way, including proteins that are important for nerve cell development."

By analyzing 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. Lead author Sebastian Waszak adds: "The latest results show that around 40 percent of children and young people who suffer from this subtype of medulloblastoma have a congenital genetic predisposition for it. That is a much higher proportion than we had assumed." Identifying hereditary causes of cancer in advance can help to make the right therapeutic decision and reduce the risk of relapse in children. "For example, in the case of a hereditary predisposition for DNA breaks, certain chemotherapies or radiotherapy can lead to secondary tumors. In such cases, the first disease should not be treated too aggressively," says Stefan Pfister.


Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

02.04.2020

Read all latest stories

Related articles

Photo

AT/RT and medulloblastoma

Promising target for treating brain tumors in children

Findings published in Oncotarget offer new hope for children with highly aggressive brain tumors like atypical teratoid/rhabdoid tumor (AT/RT) and medulloblastoma. Previously, the authors of the…

Photo

Brain cancer

Malignant Gliomas: Novel therapy may improve survival

A novel therapy engineered by Northwestern Medicine investigators improved progression-free and overall survival for patients with newly diagnosed malignant gliomas, according to results from a…

Photo

Identificación de mutaciones tumorales

El aprendizaje automático impulsa la medicina personalizada del cáncer

El laboratorio de Genómica Biomédica del IRB Barcelona (Institute for Research in Biomedicine) ha desarrollado un método computacional que identifica las mutaciones causantes del cáncer para cada…

Related products

Genrui – NE48

Extraction

Genrui – NE48

Genrui Biotech Inc.
mediaire – mdbrain

Artificial Intelligence

mediaire – mdbrain

mediaire GmbH
Orion Diagnostica Oy – Orion GenRead

Amplification

Orion Diagnostica Oy – Orion GenRead

Orion Diagnostics Oy
Subscribe to Newsletter