p53 Mutation and MDM2 amplification in human soft tissue sarcomas.
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.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
F S
FS
Leach
T
T
Tokino
P
P
Meltzer
M
M
Burrell
J D
JD
Oliner
S
S
Smith
D E
DE
Hill
D
D
Sidransky
K W
KW
Kinzler
B
B
Vogelstein
D000818:Animals; D000911:Antibodies, Monoclonal; D015139:Blotting, Southern; D002455:Cell Division / Q000502:physiology; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D015246:Deoxyribonuclease EcoRI / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008080:Liposarcoma / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D017354:Point Mutation; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D012509:Sarcoma / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D015246:Deoxyribonuclease EcoRI