PMID- 15466178 OWN - NLM STAT- MEDLINE DCOM- 20041116 LR - 20220410 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 64 IP - 19 DP - 2004 Oct 1 TI - Genetic pathways to glioblastoma: a population-based study. PG - 6892-9 AB - 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. FAU - Ohgaki, Hiroko AU - Ohgaki H AD - International Agency for Research on Cancer, Lyon, France. ohgaki@iarc.fr FAU - Dessen, Pierre AU - Dessen P FAU - Jourde, Benjamin AU - Jourde B FAU - Horstmann, Sonja AU - Horstmann S FAU - Nishikawa, Tomofumi AU - Nishikawa T FAU - Di Patre, Pier-Luigi AU - Di Patre PL FAU - Burkhard, Christoph AU - Burkhard C FAU - Schuler, Danielle AU - Schuler D FAU - Probst-Hensch, Nicole M AU - Probst-Hensch NM FAU - Maiorka, Paulo Cesar AU - Maiorka PC FAU - Baeza, Nathalie AU - Baeza N FAU - Pisani, Paola AU - Pisani P FAU - Yonekawa, Yasuhiro AU - Yonekawa Y FAU - Yasargil, M Gazi AU - Yasargil MG FAU - Lutolf, Urs M AU - Lutolf UM FAU - Kleihues, Paul AU - Kleihues P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Tumor Suppressor Proteins) RN - EC 3.1.3.2 (Phosphoric Monoester Hydrolases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Adult MH - Age Factors MH - Aged MH - Brain Neoplasms/epidemiology/*genetics/surgery MH - Cyclin-Dependent Kinase Inhibitor p16/genetics MH - Female MH - Gene Deletion MH - Genes, erbB-1/genetics MH - Genes, p53/genetics MH - Glioblastoma/epidemiology/*genetics/surgery MH - Humans MH - Incidence MH - Loss of Heterozygosity MH - Male MH - Middle Aged MH - PTEN Phosphohydrolase MH - Phosphoric Monoester Hydrolases/genetics MH - Sex Factors MH - Switzerland/epidemiology MH - Tumor Suppressor Proteins/genetics EDAT- 2004/10/07 09:00 MHDA- 2004/11/17 09:00 CRDT- 2004/10/07 09:00 PHST- 2004/10/07 09:00 [pubmed] PHST- 2004/11/17 09:00 [medline] PHST- 2004/10/07 09:00 [entrez] AID - 64/19/6892 [pii] AID - 10.1158/0008-5472.CAN-04-1337 [doi] PST - ppublish SO - Cancer Res. 2004 Oct 1;64(19):6892-9. doi: 10.1158/0008-5472.CAN-04-1337.