Childhood brain tumors: Genetic variability amenable to individualized therapy approaches
Last Updated on October 1, 2017 by Joseph Gut – thasso
October 02, 2017 – Seemingly incurable childhood brain tumor is one of the most devastating clinical diagnosis a young patient and her/his family can get. For many, the associated sufferance is close to unbearable. A better understanding of the underlying biology and genetics of these tumors is
desperately needed in order to find effective treatment options.
An important new study, just published in the journal Cancer Cell shows that deadly childhood brain tumours are actually 10 different diseases of which each could be diagnosed and classified based on their specific genetic faults. These molecular findings on the heterogeneity of brain tumors has important implications for treatment, since personalising care for each type of brain tumour is likely to be much more effective than grouping them all together as one.
In fact, a team of researchers at The Institute of Cancer Research, London, found stark differences among children’s high grade brain tumours, or gliomas, and that they could be split into at least 10 different cancer types. Many of these types of cancers have genetic mutations that could be targeted by existing drugs where some types of tumors should be far more treatable than others, depending on their genetic constellation. The researchers gathered genetic data from 910 cases from 20 previously published analyses and 157 new cases, from children or young adults up to the age of 30 with high-grade glioblastoma or diffuse intrinsic pontine glioma (DIPG).
According to the research, the tumours could be split into different subtypes based on different characteristics, such as age at diagnosis, area of the brain, the number of genetic mutations and, crucially, errors in key genes that drive these tumors. One of the striking findings from the study was that while some children’s tumours were driven by a single genetic error in which two genes were fused together, others had tens of thousands of genetic errors, among the highest number of mutations in any human cancer.
Tumors with mutations in a gene called BRAF were found to be much less aggressive than some of the other cancers, and actually shouldn’t be classified as high grade at all. These tumours could be susceptible to several adult cancer drugs that target BRAF mutations. Mutations were also found in common cancer genes such as PDGFRA, KIT, MYCN, EGFR, CDK6, and genes involved in DNA repair, all of which can be targeted by existing drugs. Numerous new potential therapeutic targets within each subtype were also detected, such as the gene TOP3A, a gene involved in DNA replication in tumours with a specific type of histone mutation called H3.3K27M. Three of the subtypes were distinguished by the presence or absence of different mutations in genes that produce histones, proteins that DNA is wrapped around to pack it tightly into cells. Histones are also involved in turning off and on certain genes, a role that can be very important in cancer. Although there are currently no drugs that can target histone mutations, there are some in development and the presence or absence of these mutations gave clues about how aggressive the cancer is, and could point to future approaches to treatment.
Overall, this study was the world’s largest of these aggressive childhood brain cancers and should lead to more accurate diagnostic tests to ensure each child receives the best possible treatment. There has been enormous support for this fundamental study as shown y the huge body of organisation who have helped to fund this study, such as the The Institute of Cancer Research (ICR), Cancer Research UK, CRIS Cancer Foundation, Abbie’s Army, The Lyla Nsouli Foundation, Christopher’s Smile, INSTINCT network funded by The Brain Tumour Charity, Great Ormond Street Hospital Children’s Charity, and Children with Cancer UK.
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