Medulloblastoma is one of the most common malignant tumors of the central nervous system (CNS) in children and adolescents. It develops in the area of the cerebellum, which is responsible for movement coordination, among other things. Medulloblastomas enlarge rapidly, often grow into surrounding tissue and can also form metastases. The wide variety of this tumor group also makes it difficult to find the right treatment.
A team of researchers at the Hopp Children’s Cancer Center Heidelberg (KiTZ), the German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD) has now investigated exactly where and when the most aggressive subgroups of these tumors develop in so-called single cell analyses. “We have genetically characterized the many thousands of individual cells from the tumor samples of numerous young patients with medulloblastoma,” explains Konstantin Okonechnikov, first author of the study from KiTZ and DKFZ. “This technology allows us to obtain a high-resolution picture of the genetic make-up within a tumor, so that we can reconstruct its developmental history fairly accurately.”
Accordingly, there are “early” and “late” genetic changes within a tumor. Based on the distribution of the genetic changes across the various tumor cell clones, the scientists were able to reconstruct the development of the tumor. The study shows that the particularly aggressive medulloblastomas of subgroups three and four probably develop between the first trimester of pregnancy and the end of the first year of life. The origin of the tumor development are the precursor cells of highly specialized nerve cells, the so-called unipolar brush cells of the cerebellum, which also develop between the first trimester of pregnancy and the end of the first year of life. Large rearrangements of entire chromosomes or chromosome arms take place in these cells, presumably initially by chance, as the present results show: The cells loose or gain certain chromosomes.
“We assume that the early loss or gain of certain chromosomes is the first step in tumor development and that these occur many years before the clinical symptoms appear,” says Lena Kutscher from KiTZ and DKFZ, who led the study together with Stefan Pfister, Director at KiTZ, Head of Department at DKFZ and paediatric oncologist at Heidelberg University Hospital (UKHD).
Only the later tumor cells carry the already known duplications or alterations of the cancer genes MYC, MYCN or PRDM6 that are typical for these types of medulloblastoma. “We therefore assume that these cancer genes are responsible for the progressive tumor growth and also for the metastasis and therapy resistance that occurs, but not for the development of the tumor,” says Lena Kutscher.
Lena Kutscher explains what these results could mean for diagnosis and treatment: “If we succeed in developing sufficiently sensitive methods in the future to detect these early changes, for example as DNA fragments in the blood, this could form the basis for possible early detection in newborns and infants.”
Original publication:
K. Okonechnikov et al.: Oncogene aberrations drive medulloblastoma progression, not initiation. In: Nature (Online Publication 7th of May 2025). DOI: 10.1038/s41586-025-08973-5
The Hopp Children’s Cancer Center Heidelberg (KiTZ)
The „Hopp Children’s Cancer Center Heidelberg” (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital and Heidelberg University. As the National Center for Tumor Diseases (NCT), which focusses on adult oncology, the KiTZ is based on the US model of so-called “Comprehensive Cancer Centers” (CCC). As a therapy and research center for oncologic and hematologic diseases in children and adolescents, the KiTZ is committed to scientifically exploring the biology of childhood cancer and to closely linking promising research approaches with patient care– from diagnosis to treatment and aftercare. Children suffering from cancer, especially those with no established therapy options, are given an individual therapy plan in the KiTZ, which is created by interdisciplinary expert groups in so-called tumor boards. Many young patients can participate in clinical trials which ensures access to new therapy options. Thus, the KiTZ is a pioneering institution for transferring research knowledge from the laboratory to the clinic.
While the KiTZ focuses on pediatric oncology, the focus of the National Center for Tumor Diseases (NCT), founded in 2004, is adult oncology. Both facilities in Heidelberg are based on the US model of so-called “Comprehensive Cancer Centers” (CCC).
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ’s Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
National Center for Tumor Diseases (NCT, 6 sites)
German Cancer Consortium (DKTK, 7 sites)
Hopp Children’s Cancer Center (KiTZ) Heidelberg
Helmholtz Institute for Translational Oncology (HI-TRON Mainz) – A Helmholtz Institute of the DKFZ
DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
Heidelberg University Hospital and Faculty of Medicine: Internationally Renowned Patient Care, Research and Teaching
Heidelberg University Hospital (Universitätsklinikum Heidelberg, UKHD) is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University (Medizinische Fakultät Heidelberg, MFHD) belongs to the internationally renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. Heidelberg University Hospital and the Medical Faculty of Heidelberg University employs around 14.500 employees and is committed to providing trainings and qualifications. Every year, around 86,000 patients and more than 1.100.000 outpatient cases are treated in more than 50 clinical departments with almost 2.500 beds.
Together with the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the German Cancer Aid, the UKHD established the first National Center for Tumor Diseases (NCT) in Heidelberg. The goal is to provide care at the highest level as an oncology center of excellence and to rapidly transfer promising approaches from cancer research to the hospital. In addition, the UKHD operates in partnership with the DKFZ and the University of Heidelberg the Hopp Children’s Cancer center Heidelberg (KiTZ), a unique and nationally known therapy and research center for oncological and hematological diseases in children and adolescents.
The Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. Currently, there are about 4.000 future physicians studying in Heidelberg.
Press contact:
Dr. Alexandra Moosmann
Head of communications KiTZ
Hopp Children’s Cancer Center Heidelberg (KiTZ)
Im Neuenheimer Feld 130.3 / 7.320
D-69120 Heidelberg
T: +49 (0) 6221 56 36434
Dr. Sibylle Kohlstädt
Strategic Communication and Public Relations
Press speaker
German Cancer Research Center
Im Neuenheimer Feld 280
D-69120 Heidelberg
T: +49 6221 42 2843
F: +49 6221 42 2968
Dr. Stefanie Seltmann
Head of Corporate Communications and Press Speaker of Heidelberg University Hospital and Medical Faculty
Im Neuenheimer Feld 672
D-69120 Heidelberg
T: +49 6221 56-5052
F: +49 6221 56-4544
E-Mail: [email protected]
www.klinikum.uni-heidelberg.de
Journal
Nature
DOI
10.1038/s41586-025-08973-5
Method of Research
Experimental study
Subject of Research
Human tissue samples
Article Title
Oncogene aberrations drive medulloblastoma progression, not initiation
Article Publication Date
7-May-2025
Media Contact
Sibylle Kohlstädt
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
Office: 49-622-142-2843
Journal
Nature
DOI
10.1038/s41586-025-08973-5
Journal
Nature
DOI
10.1038/s41586-025-08973-5
Method of Research
Experimental study
Subject of Research
Human tissue samples
Article Title
Oncogene aberrations drive medulloblastoma progression, not initiation
Article Publication Date
7-May-2025
Keywords
/Health and medicine/Human health
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Tags: aggressive cancer subgroupscentral nervous system tumorscerebellum tumor growthchildhood brain tumorsgenetic analysis of tumorsgenetic characterization of tumorsHopp Children’s Cancer Center researchmedulloblastoma researchpediatric cancer treatment challengespediatric oncology advancementssingle-cell analysis in oncologytumor development history