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Neuro-Oncology Advance Access published online on November 23, 2009
Neuro-Oncology, doi:10.1093/neuonc/nop011
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© The Author(s) 2009. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Inherited predisposition to glioma

Athanassios P. Kyritsis, Melissa L. Bondy, Jasti S. Rao and Chrissa Sioka

Neurosurgical Research Institute, University of Ioannina (A.P.K., C.S.); Department of Neurology, University Hospital of Ioannina, Ioannina, Greece (A.P.K.); Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (M.L.B.); Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois (J.S.R.); Department of Nuclear Medicine, University Hospital of Ioannina, Ioannina, Greece (C.S.)

Corresponding Author: Athanassios P. Kyritsis, MD, DSc, Department of Neurology, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece (thkyrits{at}uoi.gr).


  Abstract

In gliomas, germline gene alterations play a significant role during malignant transformation of progenitor glial cells, at least for families with occurrence of multiple cancers or with specific hereditary cancer syndromes. Scientific evidence during the last few years has revealed several constitutive genetic abnormalities that may influence glioma formation. These germline abnormalities are manifested as either gene polymorphisms or hemizygous mutations of key regulatory genes that are involved either in DNA repair or in apoptosis. Such changes, among others, include hemizygous alterations of the neurofibromatosis 1 (NF1) and p53 genes that are involved in apoptotic pathways, and alterations in multiple DNA repair genes such as mismatch repair (MMR) genes, x-ray cross-complementary genes (XRCC), and O6-methylguanine-DNA methyltransferase (MGMT) genes. Subsequent cellular changes include somatic mutations in cell cycle regulatory genes and genes involved in angiogenesis and invasion, leading eventually to tumor formation in various stages. Future molecular diagnosis may identify new genomic regions that could harbor genes important for glioma predisposition and aid in the early diagnosis of these patients and genetic counseling of their families.

Keywords: genetic predisposition, glioma, glioblastoma, polymorphism

Received January 6, 2009; Accepted March 1, 2009


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