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Researchers Categorize Incurable Childhood Brain Tumors as Separate Cancer Types

Christina Mattina
After examining over 1000 cases of high-grade gliomas in children and young adults, researchers have split these rare brain tumors into at least 10 different subtypes, which could help clinicians choose and deliver more effective treatments.
After examining over 1000 cases of high-grade gliomas in children and young adults, researchers have split these rare brain tumors into at least 10 different subtypes, which could help clinicians choose and deliver more effective treatments.

The recent study, published in Cancer Cell, analyzed 1067 new and previously published cases of pediatric glioblastoma or diffuse intrinsic pontine glioma (DIPG) in children, teens, and young adults, making it the largest such study to date. Despite their rare nature, gliomas are responsible for the greatest number of childhood cancer-related deaths, due to a lack of effective therapies resulting in a median overall survival of 9 to 15 months.

Researchers categorized each case by the tumor’s clinicopathological and molecular qualities, such as the child’s age at onset, anatomical location within the brain, and number and type of genetic mutations. They found that subtypes classified by histone mutations varied significantly in their clinical outcomes and other qualities.

For instance, H3.1K27M tumors were generally found in the pons in younger patients, who tended to have slightly longer survival. In contrast, H3.3K27M tumors were found in two-thirds of DIPG and non-brainstem midline high-grade gliomas and were associated with shorter overall survival. Researchers noted that the replication gene TOP3A seemed to play a large role in this tumor subtype, making it a potential therapeutic target.

A small number of cases (n = 11) demonstrated a significantly larger burden of mutation and were classified as “hypermutators,” compared with the median number of 12 mutations across all genome sequenced cases. These hypermutators, which had as many as tens of thousands of mutations, could be candidates for therapy with immune checkpoint inhibitors, the authors wrote.

According to a press release from the Institute of Cancer Research in London, where the researchers were based, the findings of this study “will be made available on a public data portal so the research community can use it to develop new tests and treatments.”

“Our study uncovered a wealth of new information about children’s brain cancers,” said lead study author Chris Jones, PhD, in the statement. “We found that tumours that have historically been lumped together under one diagnosis are in fact comprised of many, remarkably different, diseases.”

Jones said that a better understanding of the mutations driving each cancer would help scientists determine which types might respond to different treatments. He added that some types seemed like they would be treatable with therapies already being used for other indications or with new drugs in development.

 
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