Big Genetic Research for Small Patients

Medulloblastoma in children shows genetic basis in genes DDX3X EZH2 and KDM6A

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Children diagnosed with cancer are living longer than ever before. Some forms of the disease are essentially cured. Now, scientists are beginning to understand a tumor that's much more life-threatening.

Researchers have identified a specific genetic relationship involved in the most common kind of brain cancer in children, medulloblastoma.

Importantly, some of the identified genes are currently being targeted in other drug development efforts, which may speed the availability of new treatment opportunities for childhood brain cancer.

"Ask your oncologist about genetic based treatment."

Scientists from St. Jude Children's Research Hospital and Washington University announced that children with one type of medulloblastoma, a genetic mutation called the wingless subtype, are at little risk of death. However, with another kind of the tumor, type 3, about 60 percent of the children are alive three years after diagnosis.

The difference might be due to a mutation in a gene called DDX3X that's only present in the so-called wingless subtype of medulloblastoma. Researchers believe that this gene is a prime candidate for future medulloblastoma research.

In addition to research on drugs that can target DDX3X in medulloblastoma, researchers also discovered two other genes -- EZH2 and KDM6A -- that are involved in medulloblastoma. These genes play a role in switching on the cancer.

Both of these genes are being studied as possible targets for new drugs to attack and disable. Success in these efforts would mean new drug therapies may be available sooner for children with type 3 medulloblastoma.

"With this research we have 'lifted the lid' on the most aggressive and challenging form of medulloblastoma, subtype 3, which was really a black box in terms of our understanding, and revealed a major driver of the disease," stated Richard Gilbertson, MD, PhD, St. Jude Comprehensive Cancer Center director, and one of the study's corresponding authors.

Keith L. Black, MD, chairman of neurology at Cedars-Sinai Medical Center, told dailyRx that the research looks positive, but only future testing will reveal whether the findings were clinically significant.

“This study is a step forward in understanding key molecular steps in a childhood form of brain cancer. Whether targeting these molecular pathways with drugs results in control of these cancers is however the key question," Dr. Black writes in an email.

For the study, the complete genome of 37 children with medulloblastoma was sequenced, and the order of the DNA in their genes was compared to 56 other patients to note the differences.

Rapid advances in chemotherapy during the 1970s helped most kids (80 percent) with many cancers to beat the disease. This three-year research project was designed to look for new kinds of more specific therapy that targets the genetic changes behind each cancer.

"This study is a great example of the way whole-genome sequencing of cancer patients allows us to dig deep into the biology of certain tumors and catch a glimpse of their Achilles heel," stated the paper's co-author, Richard Wilson, PhD, the director of The Genome Institute at Washington University.

"These results help us better understand the disease and, as a result, we will be able to more effectively diagnose and treat these kids," Wilson said.

Dr. Black concludes, "Steps to translate these observations into clinical studies on the cancer will ultimately provide answers to the clinical significance of these pathways.”

This study is part of ongoing genetic research by the St. Jude Children's Research Hospital and The Genome Institute at Washington University. The Pediatric Cancer Genome Project has produced the largest whole genome sequence database in cancer research, cataloging the full DNA of over 600 children with some of the most difficult-to-treat cancers.

Findings from this research were published online June 20, 2012 in the journal Nature.

The research was funded by the Pediatric Cancer Genome Project, National Institutes of Health, the Collaborative Ependymoma Research Network, Musicians against Childhood Cancer, the Noyes Brain Tumour Foundation and the ALSAC.

Reviewed by: 
Review Date: 
June 20, 2012
Last Updated:
September 27, 2012