Influence of p53 mutations on prognosis of patients with glioblastoma

Abstract

BACKGROUNDThe influence of p53 mutations on the biology of astrocytic tumors is controversial. p53 is thought to be inactivated in the early stage of gliomagenesis; however, what role its inactivation plays in the malignancy of gliomas remains unknown. To understand the significance of p53 inactivation, the authors identified the locus of p53 gene mutation in glioma samples at different stages of progression and studied the correlation between the mutation and clinical behavior.METHODSSamples from newly diagnosed gliomas, including pure and mixed astrocytomas, were analyzed for p53 mutations using a yeast functional assay. To determine the locus of the gene mutations, DNA sequencing was performed.RESULTSThe incidence of p53 mutations was higher in anaplastic astrocytomas (AA, 48%) than glioblastomas (GBM, 31%). There was no significant difference in the average ages of GBM patients with and without p53 mutations (54.9 years ± 2.3 and 53.2 years ± 4.6, respectively). In GBM patients, the mutation did not affect progression free survival or overall survival. Astrocytomas and GBM differed in the distribution of p53 mutation loci.CONCLUSIONSThe p53 gene mutation does not markedly affect the survival of GBM patients. The difference in the location of p53 mutations between AA and GBM suggests that in gliomas, the p53 mutation may contribute not only to tumorigenesis (as an early event) but also to progression to malignancy (as a late event). Cancer 2002;95:249–57. © 2002 American Cancer Society.DOI 10.1002/cncr.10677

The Added Prognostic Value of Preoperative Dynamic Contrast-Enhanced MRI Histogram Analysis in Patients with Glioblastoma: Analysis of Overall and Progression-Free Survival

“…4,5 Molecular and genetic biomarkers of glioblastoma, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor (EGFR), p53, and Ki-67 index, are also emerging prognostic factors predicting the biologic behavior of tumors. [6][7][8][9][10] However, profiles of molecular biomarkers can only be obtained by invasive procedures such as biopsy or resection. Thus, MR imaging has been actively applied as a noninvasive tool for prognosis prediction and diagnosis and evaluation of treatment response; conventional imaging findings, such as edema, necrosis, or tumor size, have been known to be related to prognosis.…”

Single Nucleotide Polymorphism 309 Affects Murin-Double-Minute 2 Protein Expression But Not Glioma Tumorigenesis

“…All histological diagnoses were confirmed by standard histological analysis of surgical specimens as previously described. 12) Of the 254 patients, 119 had glioblastoma, 51 anaplastic astrocytoma, 13 anaplastic oligodendroglioma, 30 anaplastic oligoastrocytoma, four anaplastic ependymoma, two anaplastic ganglioglioma, 14 pilocytic astrocytoma, 12 low grade astrocytoma, four oligodendroglioma, one oligoastrocytoma, and four ganglioglioma. Genomic DNA was extracted from whole blood using the QIAamp  DNA Mini Kit (Qiagen K.K., Tokyo), dissolved in 100 ml TE (10 mM Tris and 0.5 mM ethylenediaminetetra-acetic acid), and stored at 49 C until use.…”

“…12) Briefly, using p53 PCR products from the tissues of the patients as templates, the linearized p53-expression vector pSS16 was co-transfected into the yIG397 reporter yeast strain. The transformed yeast cells were plated, incubated at 309 C for 2 days to allow the formation of colonies, and stored overnight at 49 C for color development.…”

Biomarker Discovery, Validation and Clinical Application for Patients Diagnosed with Glioma

“…The genetic profiling of large tumour cohorts with comprehensive clinical and survival data have promoted the discovery of novel molecular biomarkers associated with survival, in addition to traditional clinical and morphological features. Examples of biomarkers with prognostic significance include amplification of Epithelial Growth Factor Receptor (EGFR) (Shinojima et al 2003;Layfield et al 2006;Kaloshi et al 2007;Gan et al 2009;Inda et al 2010), over-expression of chitinase-3-like-1 (CH3L1 or YKL-40) (Hormigo et al 2006;Pelloski et al 2007), osteopontin (Sreekanthreddy et al 2010), loss of phosphatase and tensin homolog (PTEN) (Hill et al 2003;Parsa et al 2007) and mutations in the tumour suppressor protein, p53 (Shiraishi et al 2002;Ruano et al 2009). Prognostic biomarkers have great utility in the clinic.…”