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Journal of Neuro-Oncology

, Volume 110, Issue 1, pp 89–98 | Cite as

Prospective, high-throughput molecular profiling of human gliomas

  • Andrew S. ChiEmail author
  • Tracy T. Batchelor
  • Dora Dias-Santagata
  • Darrell Borger
  • Charles D. Stiles
  • Daphne L. Wang
  • William T. Curry
  • Patrick Y. Wen
  • Keith L. Ligon
  • Leif Ellisen
  • David N. Louis
  • A. John Iafrate
Clinical Study - Patient Study

Abstract

Gliomas consist of multiple histologic and molecular subtypes with different clinical phenotypes and responsiveness to treatment. However, enrollment criteria for clinical trials still largely do not take into account these underlying molecular differences. We have incorporated a high-throughput tumor genotyping program based on the ABI SNaPshot platform as well as other molecular diagnostic tests into the standard evaluation of glioma patients in order to assess whether prospective molecular profiling would allow rational patient selection onto clinical trials. From 218 gliomas we prospectively collected SNaPshot genotyping data on 68 mutated loci from 15 key cancer genes along with data from clinical assays for gene amplification (EGFR, PDGFRA, MET), 1p/19q co-deletion and MGMT promoter methylation. SNaPshot mutations and focal gene amplifications were detected in 38.5 and 47.1 % of glioblastomas, respectively. Genetic alterations in EGFR, IDH1 and PIK3CA closely matched frequencies reported in recent studies. In addition, we identified events that are rare in gliomas although are known driver mutations in other cancer types, such as mutations of AKT1, BRAF and KRAS. Patients with genetic alterations that activate signaling pathways were enrolled onto genetically selective clinical trials for malignant glioma as well as for other solid cancers. High-throughput molecular profiling incorporated into the routine clinical evaluation of glioma patients may enable the rational selection of patients for targeted therapy clinical trials and thereby improve the likelihood that such trials succeed.

Keywords

Tumor genotyping Molecular profiling Biomarker Glioblastoma Glioma 

Notes

Acknowledgments

Preliminary data of this manuscript was presented at the 2011 American Association of Neurology Annual Meeting in Honolulu, Hawaii. Andrew S. Chi is supported by a Joan Ambriz American Brain Tumor Association Basic Research Fellowship and an Early Career research award from the Ben and Catherine Ivy Foundation. Ethical Standards: All results were obtained from the medical record of patients and collected in an IRB-approved patient database. Molecular testing was performed as part of routine medical care in CLIA-certified clinical laboratories. All molecular tests comply with the current laws of the USA.

Conflicts of interest

The authors have no conflicts of interest to declare.

Supplementary material

11060_2012_938_MOESM1_ESM.pdf (142 kb)
Supplementary material 1 (PDF 142 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Andrew S. Chi
    • 1
    Email author
  • Tracy T. Batchelor
    • 1
  • Dora Dias-Santagata
    • 2
    • 3
  • Darrell Borger
    • 2
  • Charles D. Stiles
    • 4
  • Daphne L. Wang
    • 1
  • William T. Curry
    • 5
  • Patrick Y. Wen
    • 6
  • Keith L. Ligon
    • 7
  • Leif Ellisen
    • 2
  • David N. Louis
    • 3
  • A. John Iafrate
    • 2
    • 3
  1. 1.Department of Neurology, Stephen E. and Catherine Pappas Center for Neuro-OncologyMassachusetts General Hospital Cancer CenterBostonUSA
  2. 2.Translational Research LaboratoryMassachusetts General Hospital Cancer CenterBostonUSA
  3. 3.Department of PathologyMassachusetts General Hospital Cancer CenterBostonUSA
  4. 4.Department of Cancer BiologyDana-Farber Cancer InstituteBostonUSA
  5. 5.Department of NeurosurgeryMassachusetts General HospitalBostonUSA
  6. 6.Center for Neuro-Oncology, Dana-Farber/Brigham and Women’s Cancer Center and Department of NeurologyBrigham and Women’s HospitalBostonUSA
  7. 7.Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute and Department of PathologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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