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Prospective, high-throughput molecular profiling of human gliomas
Andrew S Chi1, Tracy T Batchelor, Dora Dias-Santagata
1Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. chi.andrew@mgh.harvard.edu
Journal of Neuro-Oncology
|July 24, 2012
Summary
Molecular profiling of gliomas aids in selecting patients for targeted therapy clinical trials. This approach identifies genetic alterations, improving trial success rates for malignant glioma and other cancers.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Clinical Trial Design
Background:
- Gliomas exhibit diverse molecular subtypes impacting treatment response.
- Current clinical trials often overlook these molecular distinctions, limiting patient stratification.
Purpose of the Study:
- To evaluate prospective molecular profiling for rational patient selection in glioma clinical trials.
- To integrate high-throughput genotyping into standard glioma patient evaluation.
Main Methods:
- Utilized ABI SNaPshot platform and other molecular assays for genotyping 218 gliomas.
- Assessed mutations in 68 loci across 15 cancer genes, alongside gene amplification, 1p/19q co-deletion, and MGMT methylation.
Main Results:
- Detected SNaPshot mutations in 38.5% and focal gene amplifications in 47.1% of glioblastomas.
- Confirmed frequencies of EGFR, IDH1, and PIK3CA alterations; identified rare but significant mutations (AKT1, BRAF, KRAS).
- Enrolled patients with pathway-activating genetic alterations into targeted therapy trials.
Conclusions:
- High-throughput molecular profiling in routine glioma care facilitates rational patient selection for targeted therapies.
- This strategy enhances the potential success of clinical trials for malignant gliomas and other solid tumors.
