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

Purpose Mammalian cyclin-dependent kinase inhibitors consist of two families，p16 family和p21 family.这些proteins都能证明inhibiting progression of thecell cycle by binding and inhibiting G - D21 cyclin D2 cyclin/cyclin-dependent kinase complexes. The p16gene was isolated from 9p21，一个chromosomal region that is a common site for loss of heterozygosity in many tumors，并发现mutated and homozygously deleted in many type of tumors. Therefore，p16 is regarded as one of the tumor suppressor genes. On the其他hand，p57是p21 family的成员and the gene encoding p57 is located at 11p15.5. This region is also a common site fur loss ofheterozygosity in many tumors, especially childhood tumors including Wilms' tumor，hepatoblastoma and rhabdomyosarcoma. In the current study，作者performed a mutational analysis of the p16 gene and investigated mRNA表达式p16和p57 genes in a variety of childhood malignant solid tumors.Methods：Mutational analysis was done by using polymerase chain reaction-single-strand conformationpolymorphism方法，and for mRNA表达式分析，semi-quantitative reverse transcription polymerase chain reaction method . 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）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，30% (3/19) and of the rhabdomyosarcomas.conclusions:Our data may indicate that the reduced expression of seine cyclin-dependent kinase inhibitors has arole in the pathogenesis of childhood malignant solid tumors。

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.