Ohgaki Hiroko, Dessen Pierre, Jourde Benjamin, Horstmann Sonja, Nishikawa Tomofumi, Di Patre Pier-Luigi, Burkhard Christoph, Schüler Danielle, Probst-Hensch Nicole M, Maiorka Paulo César, Baeza Nathalie, Pisani Paola, Yonekawa Yasuhiro, Yasargil M Gazi, Lütolf Urs M, Kleihues Paul
International Agency for Research on Cancer, Lyon, France.
Cancer Res. 2004 Oct 1;64(19):6892-9. doi: 10.1158/0008-5472.CAN-04-1337.
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.
我们在瑞士苏黎世州（人口116万）开展了一项基于人群的胶质母细胞瘤研究，以确定主要基因改变的频率及其对患者生存的影响。1980年至1994年间，共诊断出715例胶质母细胞瘤。经世界标准人口调整后，男性每10万人口/年的发病率为3.32，女性为2.24。观察到的6个月生存率为42.4%，1年生存率为17.7%，2年生存率为3.3%。在所有年龄组中，年轻患者的生存时间明显更长，从<50岁组的中位生存时间8.8个月到>80岁组的1.6个月不等。10号染色体长臂杂合性缺失（LOH 10q）是最常见的基因改变（69%），其次是表皮生长因子受体（EGFR）扩增（34%）、TP53突变（31%）、p16（INK4a）缺失（31%）和磷酸酶及张力蛋白同源物（PTEN）突变（24%）。LOH 10q与任何其他基因改变相关，且提示生存时间较短。原发性（新发）胶质母细胞瘤占主导（95%），而由低级别或间变性胶质瘤进展而来的继发性胶质母细胞瘤很少见（5%）。继发性胶质母细胞瘤的特征是频繁出现LOH 10q（63%）和TP53突变（65%）。继发性胶质母细胞瘤中TP53突变的57%位于热点密码子248和273，而在原发性胶质母细胞瘤中，突变分布更为均匀。继发性胶质母细胞瘤中CpG位点的G:C→A:T突变比原发性胶质母细胞瘤更常见（56%对30%；P = 0.0208）。这表明这些胶质母细胞瘤亚型中TP53突变的获得是通过不同机制发生的。
