Studies shine light on genetics of childhood brain tumours

In collaboration with the Press Association

New studies have found genes linked to two types of aggressive childhood brain tumours, and could aid the development of effective treatments.

Reported in Nature and Nature Genetics, the studies used 'next-generation' DNA sequencing technology to uncover genetic faults behind two childhood tumours that are often hard to treat - glioblastoma and diffuse intrinsic pontine glioma (DIPG).

Adult and childhood glioblastoma are thought to be caused by largely different genetic alterations, but the causes of childhood cases are less well understood.

In order to understand more about the causes, Dr Jabado, from McGill University in Montreal, and co-workers studied 48 childhood glioblastoma samples and found that 44 per cent of the tumours had faults in genes that are involved in regulating the genetic material in chromosomes.

Faults in a gene called H3F3A - which encodes a type of protein called histone H3.3 - were found in 31 per cent of tumours.

The histone H3 family of proteins are responsible for organising the DNA of every cell in the body and also for regulating the expression of the DNA code as a foetus develops.

In a second study, Suzanne Baker and co-workers at St Jude Children's Research Hospital in the US looked at DNA samples from DIPGs - a childhood tumour of the brain stem - and identified faults in two similar genes.

To start with, they sequenced the DNA from tumours and matched healthy tissues from seven children, and found mutations in two genes coding for histones H3.1 and H3.3.

They then confirmed their findings in a different set of brain tumour samples - they found that the same mutations in 39 out of 50 DIPGs and 13 out of 36 non-brainstem childhood glioblastomas.

These findings are particularly important as DIPG has a long-term survival rate of less than one in 10 and is usually inoperable because the brain stem controls essential functions such as breathing.

Dr Chris Jones, a Cancer Research UK-funded scientist from The Institute of Cancer Research said the findings were hugely significant, and shed new light on forms of cancer that are notoriously hard to treat.

"Glioblastomas are rare in children, and there have been hints that they are biologically distinct from similar tumours which arise in elderly adults," he said.

"This work demonstrates for the first time the presence of gene mutations specific to the childhood disease, particularly when the tumours arise in the brainstem, and a potentially unique way in which these tumours arise. Now much work needs to be done to turn this key biological insight into new, effective therapies for children with glioblastoma," he added.

Copyright Press Association 2012


  • Schwartzentruber, J. et al. (2012). Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma Nature DOI: 10.1038/nature10833
  • Wu, G. et al. (2012). Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas Nature Genetics DOI: 10.1038/ng.1102