Slavc I, Rodriguez I R, Mazuruk K, Chader G J, Biegel J A
Department of Pediatrics, University of Vienna, Austria.
Int J Cancer. 1997 Jul 17;72(2):277-82. doi: 10.1002/(sici)1097-0215(19970717)72:2<277::aid-ijc13>3.0.co;2-d.
Deletion of 17p is the most frequent abnormality observed in central nervous system (CNS) primitive neuroectodermal tumors (PNETs), implicating the presence of a tumor suppressor gene which maps to 17p. The gene for pigment epithelium-derived factor (PEDF) has been cloned and mapped to 17p13. PEDF belongs to the serine protease inhibitor (SERPIN) gene family. The PEDF protein has neurotrophic and neuronal-survival activities and is expressed in the CNS. Twenty tumor and matched normal DNA samples from patients with PNETs were screened by single-strand conformation polymorphism (SSCP) analysis to determine loss of heterozygosity (LOH) and to identify potential mutations within the 8 exons of the PEDF gene. Ten of the 20 tumors demonstrated LOH, consistent with the deletion status of 17p determined by cytogenetic or fluorescence in situ hybridization studies. SSCP analysis of the genomic DNA from the 10 cases with LOH demonstrated several polymorphisms in exons 4 and 7, but no mutations. Our results are consistent with a loss of alleles on 17p in 50% of CNS PNETs, but do not suggest that PEDF is a candidate for the PNET suppressor gene in 17p13.
17号染色体短臂缺失是中枢神经系统（CNS）原始神经外胚层肿瘤（PNETs）中最常见的异常情况，这意味着存在一个定位于17号染色体短臂的肿瘤抑制基因。色素上皮衍生因子（PEDF）的基因已被克隆并定位于17p13。PEDF属于丝氨酸蛋白酶抑制剂（SERPIN）基因家族。PEDF蛋白具有神经营养和神经元存活活性，并在中枢神经系统中表达。通过单链构象多态性（SSCP）分析对20例PNETs患者的肿瘤及配对正常DNA样本进行筛查，以确定杂合性缺失（LOH）并鉴定PEDF基因8个外显子内的潜在突变。20个肿瘤中有10个显示出LOH，这与细胞遗传学或荧光原位杂交研究确定的17号染色体短臂缺失状态一致。对10例存在LOH的病例的基因组DNA进行SSCP分析，结果显示外显子4和7中有几种多态性，但未发现突变。我们的结果与50%的CNS PNETs中17号染色体短臂上等位基因缺失的情况一致，但并不表明PEDF是17p13中PNET抑制基因的候选基因。
