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K. Masui, T. F. Cloughesy and P. S. Mischel (2012) Neuropathology and Applied Neurobiology 38, 271-291 Molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies The classification of malignant gliomas is moving from a morphology-based guide to a system built on molecular criteria. The development of a genomic landscape for gliomas and a better understanding of its functional consequences have led to the development of internally consistent molecular classifiers. However, development of a biologically insightful classification to guide therapy is still a work in progress. Response to targeted treatments is based not only on the presence of drugable targets, but rather on the molecular circuitry of the cells. Further, tumours are heterogeneous and change and adapt in response to drugs. Therefore, the challenge of developing molecular classifiers that provide meaningful ways to stratify patients for therapy remains a major challenge for the field. In this review, we examine the potential role of MGMT methylation, IDH1/2 mutations, 1p/19q deletions, aberrant epidermal growth factor receptor and PI3K pathways, abnormal p53/Rb pathways, cancer stem-cell markers and microRNAs as prognostic and predictive molecular markers in the setting of adult high-grade gliomas and we outline the clinically relevant subtypes of glioblastoma with genomic, transcriptomic and proteomic integrated analyses. Furthermore, we describe how these advances, especially in epidermal growth factor receptor/PI3K/mTOR signalling pathway, affect our approaches towards targeted therapy, raising new challenges and identifying new leads. [ABSTRACT FROM AUTHOR]

Presents information on the detection of brain tumors by varying methods. Identification of methods; Reference to Ga-68 EDTA PET dynamic study; Information on computer simulations; Details on the results of the simulations.

Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit from molecularly targeted therapies. Here, we address the compelling need for identification of new molecular targets. Leveraging global gene expression data from two independent sets of clinical tumor samples (n = 55 and n = 65), we identify a gene coexpression module in glioblastoma that is also present in breast cancer and significantly overlaps with the ‘metasignature’ for undifferentiated cancer. Studies in an isogenic model system demonstrate that this module is downstream of the mutant epidermal growth factor receptor, EGFRvIII, and that it can be inhibited by the epidermal growth factor receptor tyrosine kinase inhibitor Erlotinib. We identify ASPM (abnormal spindle-like microcephaly associated) as a key gene within this module and demonstrate its overexpression in glioblastoma relative to normal brain (or body tissues). Finally, we show that ASPM inhibition by siRNA-mediated knockdown inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM as a potential molecular target in glioblastoma. Our weighted gene coexpression network analysis provides a blueprint for leveraging genomic data to identify key control networks and molecular targets for glioblastoma, and the principle eluted from our work can be applied to other cancers. [ABSTRACT FROM AUTHOR]

A correction to the article "Gene expression profiling identifies molecular subtypes of gliomas," that was published in the February 2006 issue is presented.