Molecular biomarkers of glioblastoma: current targets and clinical implications

Abstract

Recent genome-wide analysis of glioblastoma has revealed various molecular alterations that can be candidate targets of biomarker findings. Although glioblastomas are diagnosed on the basis of their histopathological morphological features, it has been demonstrated that molecular heterogeneity among glioblastomas is prominent, and pathological diagnosis cannot always predict the clinical behavior of the tumor. Thus, molecular biomarkers have been anticipated to provide prognostic and predictive significance. Given that recent medical treatment strategies have been progressing toward individualized therapy and many targeted drugs have been investigated, the identification of molecular biomarkers in glioblastoma will be of considerable therapeutic importance. Although the clinical implications of these biomarkers must be determined in prospective studies, a growing number of candidate biomarkers have been investigated. In this review, the recent molecular alterations in glioblastoma that may be significant biomarkers are summarized; particular focus is on loss of heterozygosity on chromosome 10, epidermal growth factor receptor (EGFR)/EGFR variant III expression, alterations in the receptor tyrosine kinase-phosphatidylinositol 3-kinase pathway, isocitrate dehydrogenase mutation, epigenetic alterations, gene expression profiling, and microRNA expression.

Circulating biomarkers in patients with glioblastoma

“…23 Further confirmatory and descriptive tests are performed on tumour samples by using immunohistochemistry and molecular analyses, 16,[30][31][32] including the combined loss of chromosome arms 1p and 19q, the mutation and/or expression of p53, the presence of isocitrate dehydrogenase 1 (IDH1) mutation (within exon 4 to codon 132, the most common being c.395 G > A (R132H) substitutions 33 ) and epigenetic alterations, such as O 6 -methylguanine-DNA methyltransferase (MGMT) hypermethylation. 9,32 Treatment As alluded to above, current therapeutic modalities for GBM entail a combination of surgery followed by radiotherapy and/or chemotherapy. In surgery, it is challenging to safely remove all tumour cells due to the high invasive capacity of GBM cells into normal tissue; as a result, GBM tumours recur in the majority of the cases.…”