Identification of Protein Biomarkers Offers Promise for Children with Deadly Brainstem Gliomas (Funded by the Musella Foundation!)
Posted on: 04/15/2011
Identification of Protein Biomarkers Offers Promise for Children with Deadly Brainstem Gliomas
(Editor's Note: Funded by the Musella Foundation!)
Newswise — DENVER (April 13, 2011) − An estimated 4,030 new cases of childhood primary nonmalignant and malignant brain and central nervous system tumors were diagnosed in the US in 2010. Of the 4,030 new cases, an estimated 2,880 were in children younger than 15. As many as 15 percent of these pediatric brain tumors occur in the brainstem. Eighty percent of brainstem gliomas (BSG’s) are diffuse intrinsic pontine gliomas (DIPGs), an almost always fatal tumor with no effective treatment. DIPG affects young children, primarily under the age of 10, and has one of the highest mortality rates of all pediatric cancers. Current treatment is radiation therapy, but this only temporarily decreases symptoms and does not improve overall survival. Despite many clinical trials investigating new therapies, there have been no advances in DIPG treatment for over 35 years.
Researchers at Georgetown University Hospital and the Center for Genetic Medicine Research at Children’s National Medical Center in Washington, D.C., studied the biology of pediatric brainstem glioma in an effort to advance treatment of this leading cause of brain tumor death in children. The results of this study, Proteomic Profiling of Pediatric Brainstem Glioma using Cerebrospinal Fluid, will be presented by Amanda Muhs Saratsis, MD, 12:31-12:45 pm, Wednesday, April 13, during the 79th Annual Scientific Meeting of the American Association of Neurological Surgeons in Denver. Co-authors are Suresh Magge, MD, and Javad Nazarian, PhD. Dr. Saratsis will be presented with the Kenneth Shulman and WINS Louise Eisenhardt Awards for this research.
The lack of progress is due in large part to DIPG tumor tissue not being readily available for molecular study. The location and infiltrative nature of this tumor prevents surgical resection, and diagnostic biopsy is rarely performed, resulting in a lack of understanding of DIPG biology. To address this, the researchers devised an alternate approach to studying DIPG through proteomic analysis of cerebrospinal fluid (CSF).
In patients with brain tumors, CSF is in direct contact with tumor tissue. As a result, proteins secreted by a brain tumor can be detected via analysis of a patient’s CSF. Proteomic analysis allows rapid, comprehensive identification of protein content in a biological specimen, and can reveal information about tumor formation and behavior. This information can help identify tumor biomarkers for more accurate diagnosis, or lead to development of more effective treatments.
Proteomic analysis of CSF was performed on patients with BSGs, and these results were compared to the protein profile of CSF from patients with other brain tumors and healthy controls. CSF was collected during the course of patient treatment or at autopsy from 12 patients with BSGs, including 8 with DIPG, and compared to CSF from 4 healthy controls and 3 patients with non-brainstem tumors. Mass spectroscopy was used to detect, identify and quantify proteins in the CSF samples, and the resulting protein profile of each patient was analyzed. The analysis yielded the following results:
•528 total proteins were identified; multiple proteins showed different expression levels in BSG patients compared to controls, indicating abnormal protein expression patterns in tumor patients.
•Dysregulated proteins mapped to known pathways of glioma formation, neural cell migration and cell response to stress, suggesting the role of these biological pathways in DIPG formation.
•A subset of proteins was detected uniquely in DIPG samples. This supports the hypothesis that DIPG may arise due to a biologically distinct mechanism from other pediatric gliomas, and could help explain why DIPG does not respond to treatments that are effective for other tumors.
“To our knowledge, this is the first comprehensive protein profile of BSG and DIPG CSF specimens generated and shows promising potential. Further evaluation and validation using tumor tissue is underway. Proteomic analysis of CSF from children with BSG offers a systematic approach to enhancing our understanding of tumor biology and identifying unique tumor biomarkers. We hope that one day this research translates into improved outcome and survival in children affected by these devastating brain tumors,” said Dr. Saratsis.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 8,000 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.
Disclosure: the author reports no conflicts of interest. Funding has been provided by the Isabella Kerr Molina Foundation, Zickler Family Foundation, Childhood Brain Tumor Foundation, and Musella Foundation.
Media Representatives: If you would like to cover the meeting or interview a neurosurgeon − either on-site or via telephone − please contact the AANS Communications Department at (847) 378-0517 or call the Annual Meeting Press Room beginning Monday, April 11 at (303) 228-8431.
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