Anatomical localization of p53 mutated tumors: A radiographic study of human glioblastomas

Accumulating evidence has suggested that tumor location is linked to the genetic profile of gliomas. Therefore, the aim of this study was to investigate the anatomical characteristics of p53-mutated glioblastomas. We also sought to provide new insight into the possible niche locations of cells of glioblastoma origin. In order to accomplish this, preoperative magnetic resonance images from 163 patients with primary glioblastomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using the voxel-based lesion-symptom mapping approach, voxels exhibiting the strongest correlations with p53 mutants were identified. T-values of voxels that were greater than 95% of the permutations were factored into the results of the mapping analysis. Distinct anatomical characteristics between p53-mutated and wild-type glioblastomas were demonstrated using this approach. More specifically, we found that p53-mutated glioblastomas were preferentially located in the frontal lobe in the area surrounding the rostral extension of the lateral ventricles. The distinct anatomical characteristics of p53-mutated and wild-type glioblastomas provide further evidence that these gliomas arise from distinct niche locations.

[1]  R A Betensky,et al.  Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. , 2001, Cancer research.

[2]  J. Uhm.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2009 .

[3]  Daniel Y. Kimberg,et al.  Power in Voxel-based Lesion-Symptom Mapping , 2007, Journal of Cognitive Neuroscience.

[4]  Joshua M. Korn,et al.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2008, Nature.

[5]  F. Dick,et al.  Voxel-based lesion–symptom mapping , 2003, Nature Neuroscience.

[6]  Robert J. Harris,et al.  Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: A radiographic study in 358 de novo human glioblastomas , 2012, NeuroImage.

[7]  Umberto Sabatini,et al.  Neural bases of personal and extrapersonal neglect in humans. , 2007, Brain : a journal of neurology.

[8]  Zhaoshi Jiang,et al.  Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  E. Shaw,et al.  Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  L. Chin,et al.  Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. , 2006, Cancer research.

[11]  A. Álvarez-Buylla,et al.  Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes , 2010, The EMBO journal.

[12]  T. Cloughesy,et al.  Probabilistic Radiographic Atlas of Glioblastoma Phenotypes , 2013, American Journal of Neuroradiology.

[13]  Serban Nacu,et al.  A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. , 2010, Cancer cell.

[14]  Arturo Alvarez-Buylla,et al.  Mosaic Organization of Neural Stem Cells in the Adult Brain , 2007, Science.

[15]  Koji Yoshimoto,et al.  Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. , 2005, The New England journal of medicine.

[16]  S. Gabriel,et al.  Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. , 2010, Cancer cell.

[17]  A. Guha,et al.  Mouse Models to Interrogate the Implications of the Differentiation Status in the Ontogeny of Gliomas , 2011, Oncotarget.

[18]  Mitchel S Berger,et al.  Neural stem cells and the origin of gliomas. , 2005, The New England journal of medicine.

[19]  Atique U. Ahmed,et al.  Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy. , 2013, Small.

[20]  R. McLendon,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.

[21]  R. Gilbertson,et al.  Stem cells of ependymoma , 2006, British Journal of Cancer.

[22]  A. Álvarez-Buylla,et al.  Adult neural stem cells in distinct microdomains generate previously unknown interneuron types , 2013, Nature Neuroscience.

[23]  J. Uhm.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2009 .

[24]  The evolving picture of the glioblastoma genome , 2010, Oncotarget.

[25]  P. Korkolopoulou,et al.  P53 immunoexpression as a prognostic marker for human astrocytomas: a meta-analysis and review of the literature , 2010, Journal of Neuro-Oncology.

[26]  T. Jiang,et al.  Impact of p53 status to response of temozolomide in low MGMT expression glioblastomas: preliminary results , 2008, Neurological research.

[27]  Jayant P. Menon,et al.  Stem cells and the origin of gliomas: A historical reappraisal with molecular advancements , 2008, Stem cells and cloning : advances and applications.

[28]  Y. Yonekawa,et al.  Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. , 1996, Brain pathology.

[29]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.