Phelan C M, Liu L, Ruttledge M H, Müntzning K, Ridderheim P A, Collins V P
Ludwig Institute for Cancer Research, Karolinska Hospital, Stockholm, Sweden.
Hum Genet. 1995 Dec;96(6):684-90. doi: 10.1007/BF00210300.
Central nervous system (CNS) tumours are the most common solid tumours in children. Cytogenetic and molecular genetic studies of these neoplasms have previously shown abnormalities of chromosome 17, implicating genes on this autosome in tumorigenesis. To identify mutations in the TP53 tumour suppressor gene (17p13.1), we have sequenced the five highly conserved regions of this gene in 29 mixed paediatric CNS tumors. No mutations were detected by this analysis. In order to identify other candidate disease loci on chromosome 17, we have carried out a detailed deletion mapping analysis using 16 polymorphic DNA markers on 19 of the above tumours and an additional four cases. Abnormalities of chromosome 17 occurred in nine cases (39%), six of which were primitive neuroectodermal tumour (PNET)-medulloblastomas. These findings suggest that it is unlikely that the TP53 gene is directly involved in the development of common paediatric brain tumours. This is in contrast to findings from adult brain and other tumour types. Moreover, the frequency of chromosome 17 aberrations, especially in PNET-medulloblastomas, suggests that other genes on this chromosome contribute to tumourigenesis.
中枢神经系统(CNS)肿瘤是儿童最常见的实体瘤。此前对这些肿瘤的细胞遗传学和分子遗传学研究已显示17号染色体存在异常,提示该常染色体上的基因参与肿瘤发生。为了鉴定TP53肿瘤抑制基因(17p13.1)中的突变,我们对29例儿童混合性CNS肿瘤中该基因的五个高度保守区域进行了测序。该分析未检测到突变。为了鉴定17号染色体上的其他候选疾病位点,我们使用16个多态性DNA标记对上述19例肿瘤及另外4例病例进行了详细的缺失定位分析。17号染色体异常出现在9例(39%)中,其中6例为原始神经外胚层肿瘤(PNET)-髓母细胞瘤。这些发现提示TP53基因不太可能直接参与常见儿童脑肿瘤的发生。这与成人脑及其他肿瘤类型的研究结果不同。此外,17号染色体畸变的频率,尤其是在PNET-髓母细胞瘤中的频率,提示该染色体上的其他基因参与肿瘤发生。