p53 Mutation and MDM2 Amplification in Human Soft Tissue Sarcomas

FS Leach, T Tokino, P Meltzer, M Burrell, JD Oliner… - Cancer research, 1993 - AACR
FS Leach, T Tokino, P Meltzer, M Burrell, JD Oliner, S Smith, DE Hill, D Sidransky
Cancer research, 1993AACR
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 …
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.
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