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Brain tumours in children: Artificially maturing tumour cells could offer a new therapeutic approach

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(Vienna, 20 April 2018) A certain type of brain tumour, a diffuse midline glioma (DMG), occurs primarily in children of around primary school age and is difficult to treat. In an international study, in which researchers at the Department of Pediatrics and Adolescent Medicine, the Department of Neurosurgery and the Institute of Neurology, all part of the Comprehensive Cancer Center (CCC), MedUni Vienna/Vienna General Hospital played an important role, the cell architecture of this form of tumour has been analysed in more detail than ever before. The finding: a large number of cells displayed stem cell characteristics. Stem cells are immature cells, which, in contrast to normal, mature cells, divide extremely rapidly. A new therapeutic approach could therefore be to artificially mature these tumour cells, thereby halting the uncontrolled proliferation process. This study has now been published in the top journal "Science".

Tumours of the brain and spinal cord represent one quarter of all cancers in childhood and adolescence. Although advances in diagnosis and treatment have improved the prognosis for many of these cancers, Diffuse Midline Gliomas (DMG) are still incurable.

Tumour architecture
In the latest study, the researchers analysed more than 3,300 individual cells from 6 patients with a DMG, sorting the cells and then creating a genetic profile for each one. The scientists discovered that DMG develop from cells that remain in an immature, stem-cell-like state so that they divide and multiply rapidly.
 
Irene Slavc, Head of Neurooncology at the Department of Pediatrics and Adolescent Medicine of MedUni Vienna/Vienna General Hospital explains: "Our results reveal that it is the interplay of three different factors that favours the development of DMG: the characteristic mutation (H3K27M) must occur in a certain type of cell and in a specific, time-limited stage of development. An approach for intervention would be to accelerate maturation of the tumour cells by switching off the genes that code the properties of stem cells." This could be achieved by intervening in the activated signalling pathway of the tumour cells.

International and interdisciplinary collaboration
The study was conducted by an international team led by researchers from the Broad Institute of MIT and Harvard Massachusetts General Hospital (MGH) and Dana-Farber/Boston Children’s Cancer and Blood Disorder Center (DF/BC). The study was only possible due to the significant contribution made by the Department of Pediatrics and Adolescent Medicine, the Department of Neurosurgery and the Institute of Neurology at MedUni Vienna/Vienna General Hospital: half the tumour samples came from patients who had been operated on at MedUni Vienna and Vienna General Hospital. Sequencing and analysis was done by Mariella Filbin and Mario Suvaat at DF/BC in Boston, once the tumour tissue had been prepared in Vienna in collaboration with St. Anna Children's Cancer Research (CCRI). Mariella Filbin started her career at the Department of Pediatrics and Adolescent Medicine at MedUni Vienna/Vienna General Hospital. She now heads up her own research group at DF/BC.

Austria's largest interdisciplinary specialist unit at MedUni Vienna
This led to a close collaboration being established between the Department of Pediatrics and Adolescent Medicine and DF/BC, aimed at deciphering the molecular biology of paediatric brain tumours. This was possible because of the long-established and successful collaboration between the Departments of Pediatrics and Adolescent Medicine and Neurosurgery in the treatment of and research into paediatric brain tumours. Working together with the Institute of Neurology and other units of the CCC at MedUni Vienna and Vienna General Hospital, the Neurooncology Division of MedUni Vienna's Department of Pediatrics and Adolescent Medicine is the largest unit in Austria for treating childhood brain tumours.

Service: Science
“Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq” Filbin MG, Tirosh I, Hovestadt V, et al.
Science. Published online April 19, 2018. http://science.sciencemag.org/content/360/6386/331.full