Analysis of tumor-suppressor gene in pediatric malignant brain tumors

突变型p53基因产物在34%的成泥细胞瘤、22%的室管膜瘤和47%的其他胶质瘤中表达，而在包括小脑在内的正常脑组织中未发现。原位杂交分析的突变型p53基因mRNA的定位与突变型p53基因产物的定位基本一致。MIB 1指数高的组织中突变型p53基因产物表达也高。在原始神经外胚层肿瘤中，神经生长因子受体（NGF-R）在未成熟的神经源性肿瘤中表达，如髓母细胞瘤。从人髓母细胞瘤细胞系MED-3中筛选原肌球蛋白受体激酶（trk）阳性细胞亚克隆和低亲和力NGF-R阳性细胞亚克隆，检测其对NGF的反应性，发现trk阳性细胞亚克隆对NGF诱导的细胞分化有诱导作用，对NGF诱导的细胞生长有抑制作用，提示trk基因原癌基因在髓母细胞瘤分化中的作用。trk表达阳性的髓母细胞瘤预后好于trk表达阴性的髓母细胞瘤。而突变型p53基因产物的表达与预后、复发时间及对治疗的反应无关。以上结果提示trk原癌基因是髓母细胞瘤分化的靶基因。

The expression of mutant p53 gene product was found in 34% mudulloblastoma, 22% ependymoma, and 47% other gliomas in various pediatric brain tumors, although it was not found in normal brain tissues including cerebellum. And also, the localization of mRNA of mutan p53 gene analyzed by in situ hybridization was the almost same localization of mutant p53 gene product. And also, the tissues with high MIB1 index were shown the high expression of mutant p53 gene product. It was correlated between the growth potential and the expression of mutant p53 gene product.In primitive neuroectodermal tumors, nerve growth factor receptor (NGF-R) was expressed in immature neurogenic tumors, such as medulloblastoma.. We selected the subclones of tropomyosin receptor kinase (trk) -positive cells and low-affinity NGF-R-positive cells from human medullobrastoma cell line (MED-3) and examine the responsibility against NGF.Trk-positive subclone showed the induction of differentiation and the inhibition of cell growth inducd by NGF.It was suggested the role of trk gene protooncogene in differentiation of medulloblastoma. Furthermore, the prognosis in trk-positive medulloblastoma was better than that in trk-negative medulloblastoma. On the otherhand, there was no correlation between the prognosis, the period of recurrence and the responsibility against treatment and the expression of mutant p53 gene product. From the above results, it was suggested that trk protooncogene is the target gene in differentiation of medulloblastoma.