Back to Search
Start Over
Amplification of the MDM2 gene, but not expression of splice variants of MDM2 MRNA, is associated with prognosis in soft tissue sarcoma.
- Source :
-
International journal of cancer [Int J Cancer] 2001 May 20; Vol. 95 (3), pp. 168-75. - Publication Year :
- 2001
-
Abstract
- The MDM2 gene encodes a 90-kDa oncoprotein that is overexpressed in several human carcinomas, osteosarcomas, gliomas and soft tissue sarcomas (STSs). This overexpression is the result of several mechanisms, for example, enhanced transcription or translation, gene amplification and alternative splicing. We found that 19 of 67 (28.4%) STS specimens contained an amplified MDM2 gene. The amplification was more likely to be present in grade 1 tumors than in grade 2 or 3 tumors (58% of grade 1 tumors vs. 15% of grade 2 or 3 tumors, p = 0.001, chi(2) test). Furthermore, patients with tumors that contained an amplified MDM2 gene had a survival estimate (87 months) that was longer than that of patients with tumors that lacked an amplified gene (40 months; p = 0.02, log-rank test). Alternatively and aberrantly spliced MDM2 mRNAs were detected in human STSs by a highly sensitive reverse transcription-polymerase chain reaction method. Of 71 tumor samples, 38 (54%) showed evidence of the spliced forms, which included MDM2-A, MDM2-B and several variants exclusively expressed in STSs. A common feature of all forms was the absence of the MDM2 N-terminal region, which includes the TP53-binding region. Furthermore, the presence of the spliced forms was associated with elevated levels of TP53 (p = 0.01, chi(2) test). Although the presence of spliced forms was associated with late-stage tumor phenotypes (p = 0.05, chi(2) test), we observed no relationship between the presence of splice variants and patient outcome.<br /> (Copyright 2001 Wiley-Liss, Inc.)
- Subjects :
- Alleles
Genetic Markers
Humans
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-mdm2
RNA, Messenger metabolism
Sarcoma diagnosis
Survival Rate
Tumor Suppressor Protein p53 metabolism
Alternative Splicing genetics
Gene Amplification
Nuclear Proteins
Proto-Oncogene Proteins genetics
Sarcoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 95
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 11307150
- Full Text :
- https://doi.org/10.1002/1097-0215(20010520)95:3<168::aid-ijc1029>3.0.co;2-a