Daido Shigeru, Takao Soichiro, Tamiya Takashi, Ono Yasuhiro, Terada Kinya, Ito Sachio, Ouchida Mamoru, Date Isao, Ohmoto Takashi, Shimizu Kenji
Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Oncol Rep. 2004 Oct;12(4):789-95.
Certain tumor suppressor genes (TSG) residing on human chromosome 10q are implicated in astrocytic tumors. We thoroughly examined loss of heterozygosity (LOH) on chromosome 10q in astrocytic tumors to determine the extent of deletion and their relation to prognostic variables of patients. We analyzed 63 astrocytic tumors, including 9 diffuse astrocytomas, 36 anaplastic astrocytomas, and 18 glioblastomas. DNAs from tumors and leukocytes were analyzed for LOH at 18 microsatellite loci by polymerase chain reaction using fluorescence-labeled primers. Then correlation between LOH and clinicopathological variables was examined statistically. Twenty-four (66.7%) anaplastic astrocytomas and 15 (83.3%) glioblastomas had at least one LOH on chromosome 10q. However, diffuse astrocytomas exhibited no LOH. Nineteen tumors (10 anaplastic astrocytomas and 9 glioblastomas) were believed to have a total loss of one chromosome 10. Analyses on 20 tumors with interstitial LOH revealed that most of the high LOH regions matched the location of known TSGs, while some novel LOH regions were found preferentially in anaplastic astrocytoma. The median survivals of the total, partial, and no loss groups were 10.1, 14.8, and 46.8 months, respectively, indicating a significant difference in the survivals of these groups (P=0.0289). Thus, analyzing chromosome 10q loss is helpful for diagnosing malignancy in astrocytic tumors and for predicting patients' survival. Our data also suggested that there are novel TSGs for anaplastic astrocytoma at 10q24 and 10q26.
位于人类10号染色体上的某些肿瘤抑制基因(TSG)与星形细胞瘤有关。我们全面检查了星形细胞瘤中10号染色体上的杂合性缺失(LOH)情况,以确定缺失程度及其与患者预后变量的关系。我们分析了63例星形细胞瘤,包括9例弥漫性星形细胞瘤、36例间变性星形细胞瘤和18例胶质母细胞瘤。使用荧光标记引物通过聚合酶链反应分析肿瘤和白细胞的DNA在18个微卫星位点的LOH情况。然后对LOH与临床病理变量之间的相关性进行统计学检验。24例(66.7%)间变性星形细胞瘤和15例(83.3%)胶质母细胞瘤在10号染色体上至少有一处LOH。然而,弥漫性星形细胞瘤未表现出LOH。19个肿瘤(10例间变性星形细胞瘤和9例胶质母细胞瘤)被认为有一条10号染色体完全缺失。对20例存在间质LOH的肿瘤进行分析发现,大多数高LOH区域与已知TSG的位置匹配,而一些新的LOH区域在间变性星形细胞瘤中优先被发现。完全缺失组、部分缺失组和无缺失组的中位生存期分别为10.1个月、14.8个月和46.8个月,表明这些组的生存期存在显著差异(P = 0.0289)。因此,分析10号染色体缺失有助于诊断星形细胞瘤的恶性程度并预测患者的生存期。我们的数据还表明,在10q24和10q26存在间变性星形细胞瘤的新TSG。