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Multicenter Study Redefines Brain Tumor Diagnosis and Treatment 


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Key Points

  • Three groups of lower-grade glioma were captured more accurately by IDH, 1p/19q, and TP53 status than by tissue type.
  • Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes.
  • The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior similar to those found in primary glioblastoma.

Scientists at multiple institutions have found a new way of classifying brain cancers that could very well change how the illness is diagnosed and treated. The study, a project of The Cancer Genome Atlas, found striking molecular differences between various forms of gliomas by looking at the makeup of brain tumors including gene mutations, chromosomal abnormalities, and other alterations. Study findings were published in The New England Journal of Medicine.

“We found molecular signatures that better define clinical behavior based on our analysis,” said W. K. Alfred Yung, MD, Chair of Neuro-Oncology at The University of Texas MD Anderson Cancer Center. “We hope this will impact how physicians both diagnose and plan therapies for brain cancer.”

Dr. Yung and Roeland Verhaak, PhD, Associate Professor of Bioinformatics and Computational Biology at MD Anderson, were coauthors and study leads in an investigation that involved more than 300 scientists from multiple institutions.

Analysis Findings

Researchers performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression.

“We looked at the six most common forms of glioma and were able to deduce that these can be effectively grouped into three distinct molecular super clusters of lower-grade gliomas,” said Dr. Verhaak.

These three groups of lower-grade glioma were captured more accurately by IDH, 1p/19q, and TP53 status than by tissue type. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma.

“It is exciting that our findings are likely to provide a basis for the upcoming update to the World Health Organization classification of tumors of the central nervous system,” continued Dr. Verhaak.

The study represents a major step in classifying and treating brain tumors more precisely based on their genetic makeup, said Daniel J. Brat, MD, PhD, a researcher and neuropathologist at Winship Cancer Institute and coleader of the study.

The scientists believe that the use of the biomarkers in the diagnosis of these forms of brain tumors will lead to a much more consistent manner of diagnosis and patient management. The study, which involved 44 institutions, concluded that molecular tests, in addition to standard histopathological examination under the microscope, will be more accurate in indicating whether the disease is more aggressive or will respond to certain chemotherapies.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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