骨组织恶性肿瘤与癌基因mdm2、c-myc和抗癌基因p53关系的研究

Studies of mdm2 c myc oncogene and p53 antioncogene in musculoskeletal malignancies

作者采用分子分杂交技术分析了１８例骨组织恶性肿瘤及瘤旁组织中癌基因ｍｄｍ２、ｃｍｙｃ和抗癌基因ｐ５３的变化，使用ＰＣＲ－ＳＳＣＰ技术分析了ｐ５３基因第７外显子点突变，结果显示，骨组织恶性肿瘤中ｍｄｍ２、ｃｍｙｃ癌基因有扩增与过表达，抗癌基因ｐ５３有突变、重排、缺失。在１０例骨肉瘤标本中发现ｍｄｍ２扩增仅存在于转移的病例中。这些结果表明：癌基因ｍｄｍ２、ｃｍｙｃ与抗癌基因ｐ５３参与骨组织恶性肿瘤的发生和发展，其中ｍｄｍ２扩增与骨肉瘤转移密切相关。

Eighteen couple samples of musculoskeletal malignancies and para tumor tissues were screened for alteration on mdm2 c myc and p53 by hybridizations of Southern blot and Dot blot,and for point mutations of exon 7 of p53 by PCR-SSCP. The result of Southern blot showed that,4 samples of musculoskeletal tumors were found for mdm2 amplifications,3 of which were osteosarcomas, 1 malignant fibrohistoblastoma, 4 samples of the tumors and 1 sample of para tumor tissues were found for c myc amplifications;4 samples of the tumors and 2 samples of para tumor tissues were found to have the rearrangements of p53 gene, 1 of which had part deletion. The result of RNA Dot blot showed that, all samples were found to have high expressions of mdm2 gene , and statistical significance was revealed throught examination, P<0.01, and expression of tumor samples were much more than para tumor tissues; 10 samples of tumors have high expressions of c myc gena, 8 samples had low expressions, 1 sample of tumor had high expression of p53, 2 had no expression, 15 had low expression.6 samples of tumors were found to have mutations of p53 by PCR-SSCP. Combining with the clinical data, mdm2 amplifications were only found in metastasis samples of 10 samples of osteosarcoma. The authors concluded that, in the musculoskeletal tumors, the mdm2 oncogene is activated by mutation and amplification, the c myc by amplification and the p53 is inactivated by mutation rearrangement and deletion.These genes are all involved in the progressive growth of musculoskeletal tumors; in the musculoskeletal tumor, mdm2 gene amplification does not coexist with p53 gene alteration, and mdm2 amplification is closely associated with osteosarcoma metastasis. The screening for mdm2 amplification may be a useful prognostic indicator for osteosarcoma.