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PMID: 8387391 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

p53 Mutation and MDM2 amplification in human soft tissue sarcomas.

Cancer research ·Vol. 53 ·No. 10 Suppl ·1993-05-15 ·Pages 2231-4

Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW, Vogelstein B

Abstract

The p53 and MDM2 genes were analyzed in 24 human soft tissue sarcomas (11 malignant fibrous histiocytomas and 13 liposarcomas). Alterations of p53, consisting of point mutations, deletions, or overexpression, were detected in one-third (8 of 24) of the sarcomas. MDM2 gene amplification was detected in another 8 tumors, but no tumor contained an alteration of both genes. Monoclonal antibodies reactive with the human MDM2 gene product were developed, and immunohistochemical analysis revealed nuclear localization and overexpression of MDM2 in those tumors with amplified MDM2 genes. These data support the hypothesis that p53 and MDM2 genetic alterations are alternative mechanisms for inactivating the same regulatory pathway for suppressing cell growth.

Related Genes
MDM2 p53
MeSH Terms
Animals Antibodies, Monoclonal Blotting, Southern Cell Division/physiology DNA Probes DNA, Neoplasm/genetics Deoxyribonuclease EcoRI/metabolism Exons/genetics Female Gene Amplification/genetics Gene Expression/genetics Genes, p53/genetics Histiocytoma, Benign Fibrous/genetics Humans Immunohistochemistry Liposarcoma/genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Neoplasm Proteins/genetics Nuclear Proteins Point Mutation Proto-Oncogene Proteins Proto-Oncogene Proteins c-mdm2 Sarcoma/genetics Soft Tissue Neoplasms/genetics Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal DNA Probes DNA, Neoplasm Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins MDM2 protein, human Mdm2 protein, mouse Proto-Oncogene Proteins c-mdm2 Deoxyribonuclease EcoRI
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Leach F S
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Tokino T
Meltzer P
Burrell M
Oliner J D
Smith S
Hill D E
Sidransky D
Kinzler K W
Vogelstein B
Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
0008-5472
Published
1993-05-15
Pages
2231-4
Language
English
Region
United States
NLM ID
2984705R
Subset
IM
Grants
NCI NIH HHS · CA35494 · United States
NCI NIH HHS · CA43460 · United States
NIGMS NIH HHS · GM07184 · United States
External Links
PubMed source View journal details
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