Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas Journal Article
| Authors: | Cordon-Cardo, C.; Latres, E.; Drobnjak, M.; Oliva, M. R.; Pollack, D.; Woodruff, J. M.; Marechal, V.; Chen, J.; Brennan, M. F.; Levine, A. J. |
| Article Title: | Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas |
| Abstract: | Genetic alterations in the p53 and mdml genes have been reported to occur in soft tissue sarcomas. This study was designed to determine the prevalence and potential clinical value of detected molecular abnormalities and altered patterns of expression of mdml and p53 genes in adult soft tissue sarcomas. A cohort of 211 soft tissue sarcomas from adults that were both clinically and pathologically well characterized was analyzed. Monoclonal antibodies directed against mdm2 and p53 proteins were used to measure overexpression of these proteins in the nuclei of cells from sections of these tumors. Seventy-six of 207 tumors had abnormally high levels of mdm2 proteins and 56 of 211 tumors overexpressed p53 protein. Twenty-two cases had abnormally high levels of both mdm2 and p53 proteins based upon immunoreactivity with these antibodies. There was a striking statistically significant correlation between the overexpression of p53 and mdm2 proteins in the same tumor and poor survival (P < 0.05) of the patients. A group of 73 soft tissue sarcomas was chosen for analysis using Southern blots, single strand conformation polymorphisms, and direct DNA sequencing to confirm mdml gene amplifications and p53 mutations and correlate these with the results of the immunoreactivities. The overexpression of p53 and mdm2 proteins in the nuclei of tumor cells did not always correlate well with gene amplification at the mdml locus or mutation at the p53 gene. The possible reasons for these discrepancies are discussed. © 1994, American Association for Cancer Research. All rights reserved. |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; gene mutation; major clinical study; gene deletion; proto-oncogene proteins; histopathology; molecular genetics; phenotype; cohort studies; gene amplification; gene expression; neoplasm proteins; genotype; immunoreactivity; protein p53; nuclear proteins; monoclonal antibody; sarcoma; gene expression regulation; tumor suppressor gene; dna; dna, neoplasm; soft tissue sarcoma; dna sequence; cell nucleus; point mutation; analysis of variance; soft tissue neoplasms; complementary dna; deletion mutant; proto-oncogene proteins c-mdm2; genes, p53; protein antibody; southern blotting; restriction fragment length polymorphism; humans; human; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 54 |
| Issue: | 3 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1994-01-01 |
| Start Page: | 794 |
| End Page: | 799 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8306343 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
Citation Impact
Related MSK Work