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Update on molecular findings, management and outcome in low-grade gliomas

Nature Reviews Neurology volume 6, pages 695–701 (2010)Cite this article

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Abstract

Low-grade infiltrating gliomas in adults include diffuse astrocytoma, oligoastrocytoma and oligodendroglioma. The current gold standard diagnosis of these tumors relies on histological classification; however, emerging molecular abnormalities discovered in these tumors are playing an increasingly prominent part in the process of tumor diagnosis and, consequently, patient management. The frequency and clinical importance of tumor protein p53 (TP53) abnormalities, deletions involving chromosomes 1p and 19q, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, abnormalities in the PTEN tumor suppressor gene and the BRAF oncogene, and isocitrate dehydrogenase (IDH) mutations have become better defined. Molecular markers have not, historically, had an important role in determining the course of treatment for patients with low-grade gliomas, but ongoing phase III clinical trials incorporate 1p deletion or 1p19q codeletion status—and future trials plan to incorporate MGMT promoter methylation status—as stratification factors. Future trials will need to incorporate IDH mutational status in addition to these factors. Ultimately, molecular marker assessment will, hopefully, improve the accuracy of tumor diagnosis and enhance the effectiveness of treatment to achieve improved patient outcomes.

Key Points

  • Isocitrate dehydrogenase (IDH) mutations seem to occur earlier than tumor protein p53 (TP53) mutations or deletions of chromosomes 1p and/or 19q among a subset of diffuse astrocytomas and oligodendroglial tumors

  • Tumors with 1p and/or 19q chromosomal deletions usually also have IDH mutations

  • 1p19q codeletion and IDH mutation each have favorable prognostic value, with IDH-mutated, 1p19q-intact tumors having an outcome intermediate between 1p19q-codeleted tumors and tumors that lack either of these molecular markers

  • The independent prognostic importance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation remains to be determined

  • No molecular marker has yet been validated as predicting a favorable response to chemotherapy or radiation therapy

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Figure 1: A model for the development and progression of astrocytic and oligodendroglial tumors.

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  1. Department of Pathology, Division of Neuropathology, University of Virginia Health System, Box 800214, Charlottesville, 22908-0214, VA, USA

    T. David Bourne

  2. Division of Neuro-oncology, University of Virginia Health System, 1300 Jefferson Park Avenue, Box 800432, Charlottesville, 22908-0432, VA, USA

    David Schiff

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T. D. Bourne and D. Schiff both contributed equally to this work in terms of research, writing, editing and reviewing.

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Bourne, T., Schiff, D. Update on molecular findings, management and outcome in low-grade gliomas. Nat Rev Neurol 6, 695–701 (2010). https://doi.org/10.1038/nrneurol.2010.159

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