Mutation and Expression Analyses of Cycin-Dependent Kinase Inhibitor Gene, p571KIP2 in Childhood Malignant Solid Tumors

目的哺乳动物环素依赖激酶抑制剂的两个家族、一个p16家族和一个p21家族。These Proteins are all capable of inhibiting progression of the cell cycle by binding and inhibiting G-D21 cyclin/cyclin-dependent kinase complexes。p16基因从9 p21分离，是一个染色体区域，它是一个常见的位点，在许多肿瘤中失去异质性，并找到了在许多肿瘤类型中被突变和均匀地删除。因此，第16页被归类为肿瘤抑制剂的一种。在另一边，第57页是p21家族的成员，基因编码第57页位于11页15.5。这一地区也是多种肿瘤、特别是儿童肿瘤，包括Wilms'肿瘤、Hepatoblastoma和rhabdomyosarcoma的常见站点缺陷。在目前的研究中，作者对p16基因和受试mRNA表达的p16和p57基因在不同种类的儿童恶性肿瘤固体肿瘤中进行了相互分析。方法：使用聚合酶链反应-单链结构聚合酶方法进行了相互分析，以及mRNA表达分析、半定量反向转录聚合酶链反应方法使用。结果：在111个肿瘤中分析了，检测到了无恶性相关突变。However，在威尔姆斯肿瘤中发现了42%（5/12）的P16基因和40%（4/10）的淋巴瘤。Moreover，对p57基因的减少表达也在14%（2/14）的神经分裂症、21%（3/14）的肝细胞肿瘤、25%（3/12）的威尔姆斯肿瘤和30%（3/19）的神经分裂症。我们的数据可以表明，seine cyclin-dependent kinase抑制剂的减少表达在儿童恶性肿瘤固体肿瘤的病理学中起着作用。

Purpose Mammalian cyclin-dependent kinase inhibitors consist of two families, the p16 family and the p21 family. These proteins are all capable of inhibiting progression of the cell cycle by binding and inhibiting GィイD21ィエD2 cyclin/cyclin-dependent kinase complexes. The p16 gene was isolated from 9p21, a chromosomal region that is a common site for loss of heterozygosity in many tumors, and found to be mutated and homozygously deleted in many types of tumors. Therefore, p16 is regarded as one of the tumor suppressor genes. On the other hand, p57 is a member of the p21 family, and the gene encoding p57 is located at 11p15.5. This region is also a common site fur loss of heterozygosity in many tumors, especially childhood tumors including Wilms' tumor, hepatoblastoma and rhabdomyosarcoma. In the current study, the author performed a mutational analysis of the p16 gene and investigated mRNA expression of the p16 and p57 genes in a variety of childhood malignant solid tumors.Methods : Mutational analysis was done by using polymerase chain reaction-single-strand conformation polymorphism method, and for mRNA expression analyses, semi-quantitative reverse transcription polymerase chain reaction method was used.Results : Among 111 tumors analyzed, no malignancy associated mutation was detected. However, reduced expression of the p16 gene was found in 42% (5/12) of the Wilms' tumors and 40% (4/10) of the rhabdomyosarcomas. Moreover, reduced expression of the p57 gene was also observed in 14%(2/14)of the neuroblastomas, 21% (3/14) of the hepatoblastomas, 25% (3/12) of the Wilms' tumors, and 30% (3/19) of the rhabdomyosarcomas.Conclusions : Our data may indicate that the reduced expression of seine cyclin-dependent kinase inhibitors has a role in the pathogenesis of childhood malignant solid tumors.