大肠癌患者及其家族成员外周血淋巴细胞p53基因突变研究

p53 GENE MUTATION OF PERIPHERAL LYMPHOCYTES IN PATIENTS WITH LARGE BOWEL CARCINOMA AND THEIR FAMILIAL MEMBERS

本文应用聚合酶链反应———单链构象多态（ＰＣＲ－ＳＳＣＰ）银染技术对２０例大肠癌患者和２０例大肠癌家庭成员的外周血淋巴细胞ｐ５３基因第５，６，７和８外显子进行检测，发现有６例大肠癌患者和５例家族成员存在基因突变；突变率分别为３０％和２５％。这一结果表明ｐ５３基因突变在大肠癌中的普遍存在，并在大肠癌的发生过程中起着重要作用；而家族成员中发现ｐ５３基因突变将可为癌症的癌前监控和预防提供重要佐证。

Using PCR SSCP silver staining technique,20 patients with large bowel cancer (LBC),and 20 their familial members (FM) were analysed for mutation in exons 5-8 of p53 gene of peripheral lymphocytes. Among them,p53 mutation were found in 6 cases with LBC and in 5 cases with FM. The mutation rates were 30% and 25% in LBC and FM,respectively. It was \ mation of infinite life span human cell strain by transfection with v-Ki-ras.Oncogene,1990;5:1415. 6\ Yang D,Louden C,Reinhold DS,et al.Malignant transformation of human fibroblast cell strain MSU-1.1 by(±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-etrahydrobenzo(a)pyrene.Proc Natl Acad Sci USA,1992;89:2237. 7\ Ryan PA,Maher VM,McCormick JJ.Modification of MCDB 110 medium to support prolonged growth and consistent high cloning efficiency of diploid human fibroblasts.Exp Cell Res,1987;172:318. 8\ Namba M,Bai L,Kondo T, et al. Immortalization and neoplastic transfomation of normal human fibrolasts with 4-nitroquinoline-1-oxide and c-Ha-ras oncogene.Proc Int Symp on Cell Transformation.Mackinac Island,MI,1993. 9\ Clark R,Stampfer MR,Milley R,et al.Transformation of human breast epithelial cell by c-Ha-ras oncogene.Mol Carcinogen,1990;50:4724. 10\ Williams AC,Harper SJ,Paraskeva C,et al. Neoplastic transformation of human colonic epithelial cell line:in vitro evidence for the adenoma to carcinoma sequence.Cancer Res,1990;50:4724. 11\ Vogelstein B,Fearon BA,Hamilton SR, et al. Genetic alternations during colorectal tumor development.New Eng J of Med,1988;319:525.showed that p53 gene mutation is a common event in LBC, which plays an important role in the progression of LBC. Our preliminary study indicates the detecting of p53 gene mutation may be used as a molecule diagnosis for susceptible individuals of LBC.