Genetic Pathways to Glioblastoma

2004/10/01 by Hiroko Ohgaki, Pierre Dessen, Benjamin Jourde +19 · 1,262 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Allele #Apoptosis #Biology #Cancer Genomics and Diagnostics #Cancer research #Cancer-related Molecular Pathways #Gene #Genetics #Glioma Diagnosis and Treatment #Internal medicine #Loss of heterozygosity #Medicine #Oncology #PTEN #Population

paper · pdf · doi:10.1158/0008-5472.can-04-1337

published in Cancer Research 64(19), 6892-6899 (American Association for Cancer Research)

openalex publication_date 2004/10/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/05

Abstract

We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (<50 years) to 1.6 months (>80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

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