New genes provide insight for rare brain tumour

A new study, published in the Nature journal, has provided more insight into one of the deadliest forms of paediatric brain tumour - Group 3 medulloblastoma.

It is often linked to a variety of large-scale DNA rearrangements that have a similar effect on specific genes located on different chromosomes. Previously, only a gene called MYC was known to play a key role in the development of Group 3 medulloblastoma, but this did not explain all of the characteristics of this type of brain tumour. 

Researchers at the European Molecular Biology Laboratory (EMBL) and the German Cancer Research Centre (DKFZ), both in Heidelberg, Germany, and Sanford-Burnham Medical Research Institute in San Diego, USA, wanted to identify what other genes were involved.

This type of medulloblastoma has a higher metastasis rate and overall poorer prognosis than other brain tumours in children. In order to find the answer, Dr Jan Korbel's group at EMBL, along with colleagues at DKFZ,  took advantage of the large number of medulloblastoma genome sequences known to find new genes involved.

Dr Kornel said the team had been surprised to find two other major drivers of Group 3 medulloblastoma, along with MYC. The discovery of these sister genes - GFI1B and GFI1 - could aid research into treatment for other cancers, as the team found these genes had been "activated in a way that cancer researchers don’t usually look for in solid tumours".

They took a novel approach to try and identify the changes in each gene as the team focused on large-scale rearrangements of the stretches of DNA that lie between genes, rather than adopting the standard approach.

“Nobody has seen such a process in solid cancers before,” said Dr Paul Northcott from DKFZ, “although it shares similarities with a phenomenon implicated in leukaemias, which has been known since the 80s.”

Their research found that the DNA of different patients showed evidence of different rearrangements: duplications, deletions, inversions, and even complex alterations involving many ‘DNA-shuffling’ events.