12 August 2008

Australian and American scientists have identified the origins of the most malignant type of brain tumour in a discovery that could lead to better therapies and improve our understanding of how tumours initiate.

The team, led by Professor Brandon Wainwright from the Institute for Molecular Bioscience at the University of Queensland in Brisbane, Australia, and Dr Robert Wechsler-Reya from Duke University in Durham, USA, studied medulloblastomas, which occur most often in children.

“Almost half the people who develop these tumours die from them, and those who survive often suffer severe side effects from the treatment,” Professor Wainwright said. “Improved treatments are urgently required, but in order to develop these, we need a deeper understanding of the molecular and cellular origins of medulloblastomas.”

The team found that medulloblastomas can originate from two types of cell: multipotent neural stem cells (NSCs) and granule neuron precursors (GNPs). NSCs are stem cells that can become most types of cell within the nervous system, while GNPs are similar to stem cells but only give rise to one type of cells, known as granule neurons.

“There was good evidence that either cell type could be the origin of medulloblastomas, but no one considered that both sets of evidence could be correct, and that these tumours could actually begin in two different cell types,” Professor Wainwright said.

“Identifying the normal cell that gives rise to a tumour is important because it allows direct comparisons between tumour cells and their normal counterparts so that key differences and vulnerabilities in the tumour can be identified.

“Also, recent studies suggest that cells resembling the original cell may persist in mature tumours and can be critical in ensuring its survival. If so, these cells would be an excellent target for treatment.”

The team made their discovery by examining a gene called Patched, which is involved in the regulation of both neural stem cells and GNPs. When the gene is inactivated, medulloblastomas develop.

However, when inactivation occurs, it happens in all cells, so there was no way of knowing in which cell the tumour had begun. The team took advantage of an allele, or version, of Patched that allows inactivation of the gene in either GNPs or neural stem cells, and found that the tumours developed no matter in which cell Patched was inactivated.

The study could also have wider implications for treating other types of cancer, as the team also found that cancer doesn't always originate in the same way.

“It has always been thought that cells had to mutate several times before becoming a tumour,” Professor Wainwright said. “In this study we found that some stem cells only needed to mutate once.

“They would not turn cancerous immediately, but once they had been given an instruction to turn into a more specialised cell, the mutation would take hold and they would instead turn into a tumour.”

The study has been published in current issue of leading scientific journal Cancer Cell, and is funded by the National Health and Medical Research Council, the Australian Cancer Research Foundation, the Cancer Council QLD and the John Trivett Foundation.

Media contacts:

Professor Brandon Wainwright – 07 3346 2110

Bronwyn Adams, IMB Communications – 07 3346 2134 or 0418 575 247

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