New study shows that genomic profiling can help improve treatment of brain tumors in children

September 14, 2017

The largest genomic profiling study ever conducted into a type of brain tumor known as glioma in children has identified genetic alterations in 96% of cases. As reported in The Oncologist, this genetic information could help to identify the most effective treatments for specific cases of glioma, hopefully improving the prognosis for what is currently the leading cause of death for children with cancer in the US.

"This study further demonstrates that can be readily integrated into the routine clinical workflow for children with brain tumors," says corresponding author Shakti Ramkissoon, associate medical director at Foundation Medicine, a genomic profiling company based in Cambridge, MA. "We hope that the collection of objective genomic data will one day become 'standard of care' for children with brain tumors."

Pediatric gliomas are a diverse collection of affecting children that arise from glial cells in the brain and spinal cord. Despite their diversity, pediatric gliomas can be categorized into two broad classes: low-grade gliomas (LGGs) and (HGGs), with LGGs more benign and less malignant than HGGs. Nevertheless, treatment options for both LGGs and HGGs are limited, and the long-term prognosis for children with is not good. Anything that can improve this prognosis is thus to be welcomed.

With this aim in mind, Ramkissoon and a team of scientists from Foundation Medicine and several universities and medical centers in the US conducted genomic profiling of 125 LGGs and 157 HGGs taken from varying in age from less than one to 18. To do this, they employed a technique termed hydridization-captured, ligation-based sequencing. This involves extracting DNA from each tumour sample and then introducing it to a chip covered in short strands of synthetic DNA able to capture sequences from 315 cancer-related and 28 genes commonly rearranged in cancer.

Captured DNA is then sequenced on the chip to determine which of these genes are altered and how they are altered. These alterations can include mutations to single genes, where DNA sequences are rearranged, deleted or inserted, and the fusing together of several genes.

Ramkissoon and his team detected in 96% of the tumor samples, with the most frequently altered genes differing between LGGs and HGGs. They found that genes known as BRAF, FGRFR1 and NF1 were most frequently altered in LGGs, whereas genes known as TP53 and H3F3A, together with NF1 again, were most frequently altered in HGGs. Not only does this finding show that genomic profiling can distinguish between different gliomas, but it also confirms that genomic profiling can help identify the most effective treatments for those different gliomas.

"Our findings highlight the importance of identifying mutations that have been shown to be diagnostically and prognostically significant," says Ramkissoon. "For example there is strong evidence to show that LGGs harbouring BRAF fusions have significantly better outcomes compared to LGGs with BRAF mutations; therefore, determining the BRAF status for all pediatric LGGs is important for clinical management. Additionally, our findings identify targets for targeted therapies and highlight the utility of small molecule inhibitors for the treatment of recurrent pediatric gliomas."

Thus this study shows that BRAF-inhibitors such as dabrafenib, which are currently undergoing clinical trials for treating pediatric gliomas, are likely to be more effective against LGGs than HGGs. It also shows that targeting H3F3A mutations could offer an effective way to treat HGGs. Furthermore, Ramkissoon and his team found that nine of the HGGs had a particularly high number of mutations, known as a high mutation burden, which previous research has indicated responds well to immunotherapy.

Building on this work, Ramkissoon and his team are next planning to conduct a genomic profiling study of a type of known as a glioblastoma in young adults, aged between 18 and 40.

"Pediatric gliomas represent a truly unmet clinical need in oncology. This work demonstrates that molecular profiling of these tumors provides potential therapeutic opportunities for these patients, including targeted therapies and immune checkpoint inhibitors," says Priscilla Brastianos, director of the Central Nervous System Metastasis Program at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, who is a section editor of The Oncologist and was not involved in the study.

Explore further: Genetic mutations help brain tumors evade targeting by immunotherapy treatments

More information: The Oncologist (2017). DOI: 10.1634/theoncologist.2017-0242

Related Stories

Genetic mutations help brain tumors evade targeting by immunotherapy treatments

March 20, 2017
Tumors of the brain and spinal cord, or gliomas, are among the most commonly occurring brain tumors. Although a majority of gliomas are classified as curable, these low-grade tumors have the potential to develop more aggressive ...

Whole genome sequencing finds new mutations to blame for a majority of brain tumor subtype

April 14, 2013
Washington University Pediatric Cancer Genome Project has identified mutations responsible for more than half of a subtype of childhood brain tumor that takes a high toll on patients. Researchers also found evidence the tumors ...

Gene sequencing project finds new mutations to blame for a majority of brain tumor subtype

May 30, 2013
(Medical Xpress)—The St. Jude Children's Research Hospital – Washington University Pediatric Cancer Genome Project has identified mutations responsible for more than half of a subtype of childhood brain tumor that takes ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Next-generation sequencing test identified potential targets for pediatric cancer treatments

November 5, 2013
A comprehensive genomic profiling test using next-generation sequencing has identified genomic alterations in more than half of pediatric cancer samples tested that would give clinicians potential targets on which to base ...

Genome-wide data can classify gliomas into subtypes

June 11, 2015
(HealthDay)—Genome-wide data can help classify subtypes of gliomas, according to two studies published online June 10 in the New England Journal of Medicine.

Recommended for you

New strategy for unleashing cancer-fighting power of p53 gene

December 13, 2017
Tumor protein p53 is one of the most critical determinants of the fate of cancer cells, as it can determine whether a cell lives or dies in response to stress. In a new study published today in the journal Nature Communications, ...

Researchers develop test that can diagnose two cancer types

December 12, 2017
A blood test using infrared spectroscopy can be used to diagnose two types of cancer, lymphoma and melanoma, according to a study led by Georgia State University.

Cancer-causing mutation suppresses immune system around tumours

December 12, 2017
Mutations in 'Ras' genes, which drive 25% of human cancers by causing tumour cells to grow, multiply and spread, can also protect cancer cells from the immune system, finds a new study from the Francis Crick Institute and ...

Atoh1, a potential Achilles' heel of Sonic Hedgehog medulloblastoma

December 12, 2017
Medulloblastoma is the most common type of solid brain tumor in children. Current treatments offer limited success and may leave patients with severe neurological side effects, including psychiatric disorders, growth retardation ...

MRI scans predict patients' ability to fight the spread of cancer

December 12, 2017
A simple, non-invasive procedure that can indicate how long patients with cancer that has spread to the brain might survive and whether they are likely to respond to immunotherapy has been developed by researchers in Liverpool.

Drug suppresses spread of breast cancer caused by stem-like cells

December 12, 2017
Rare stem-like tumor cells play a critical role in the spread of breast cancer, but a vulnerability in the pathway that powers them offers a strategy to target these cells using existing drugs before metastatic disease occurs, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.