Molecular markers of gliomas

M. Eoli, A. Di Stefano, G. Finocchiaro

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In parallel to the increasing amount of information on the molecular biology of gliomas, novel markers of clinical interest have become available. Loss of heterozygosity (LOH) studies were the first to provide such markers. LOH on 1p and 19q, in particular, appeared as associated with chemosensitivity in oligodendrogliomas and mixed gliomas; because of this, their investigation became increasingly popular in clinical trials on gliomas. Even more relevant in the clinical practice is the assessment of the methylation of regulatory regions of the methyl-guanine methyl-transferase (MGMT) gene. Seminal studies by Esteller et al. established that MGMT methylation is present in about 40% of glioblastomas (GBM); these are the patients with increased survival, and subsequent studies by Hegi et al. proposed that this is due to increased chemosensitivity, particularly to temozolomide. Thus, MGMT methylation is presently a major criterion for stratification of patients with malignant gliomas enrolled in clinical trials. Also of relevance in gliomas are three other markers: EGFR, p53, and PTEN. Amplification and/or deletion of EGFR are present in GBM originating de novo and may be therapeutic targets, p53 mutations, in contrast, are present in secondary GBM, and PTEN mutations are present in both types of GBM and may help to pinpoint a patient subgroup responding to erlotinib. In this chapter, we try to re-assess the role of all these markers, based on the most recent literature. We also focus on more recent markers and on their relationships to that fraction of glioma cells that express stem cell genes like CD133. This fraction of tumor cells, defined as cancer stem cells, may have a key role in cancer perpetuation; their assessment, therefore, can be very important for prognosis and therapy. Clearly; what we will have is a snapshot of a highly dynamic landscape. The ongoing effort to sequence the genome of several hundred GBM will undoubtedly make this area of research ripe for significant changes in the clinical handling of this devastating disease.

Original languageEnglish
Title of host publicationTherapeutic Ribonucleic Acids in Brain Tumors
PublisherSpringer-Verlag Berlin Heidelberg
Pages157-177
Number of pages21
ISBN (Print)9783642004759, 9783642004742
DOIs
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Eoli, M., Di Stefano, A., & Finocchiaro, G. (2009). Molecular markers of gliomas. In Therapeutic Ribonucleic Acids in Brain Tumors (pp. 157-177). Springer-Verlag Berlin Heidelberg. https://doi.org/10.1007/978-3-642-00475-9_8