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Update on molecular findings, management and outcome in low-grade gliomas
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Update on molecular findings, management and outcome in low-grade gliomas
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Journal Article
Update on molecular findings, management and outcome in low-grade gliomas
2010
Overview
Diagnosis of low-grade inflitrating gliomas—a class of brain tumors that includes diffuse astrocytoma, oligoastrocytoma and oligodendroglioma—currently relies largely on histological classification, although molecular discoveries are beginning to generate new paradigms for diagnosis and management. Bourne and Schiff highlight the molecular abnormalities that have been identified in low-grade gliomas, and discuss how factors such as chromosome 1p19q codeletion and
MGMT
promoter methylation status are facilitating stratification of patients in clinical trials.
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,
O
6
-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
O
6
-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
