Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas

Patterson, H., Gill, S., Fisher, C., Law, M. G., Jayatilake, H., Fletcher, C. D.M., Thomas, M., Grimer, R., Gusterson, B. A. and Cooper, C. S. ORCID: https://orcid.org/0000-0003-2013-8042 (1994) Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas. British Journal of Cancer, 69 (6). pp. 1052-1058. ISSN 0007-0920

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In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.

Item Type: Article
Additional Information: Funding Information: The probes pDCCl.0, pDCCl.65, JOSH4.4 and SAM1.l were a kind gift from Professor Bert Vogelstein. The polymorphic probe OLVIIEIO was kindly donated by Dr Gilles Thomas, and the MDM2 probe by Dr Alasdair Stamps. The p53 monoclonal antibody was a gift from Dr David Lane. We would like to thank Deborah Eagle for help in collating the clinical data. This work is supported by grants from the Cancer Research Campaign and Medical Research Council.
Uncontrolled Keywords: oncology,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
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Depositing User: LivePure Connector
Date Deposited: 18 Jul 2022 16:31
Last Modified: 23 Oct 2022 04:01
URI: https://ueaeprints.uea.ac.uk/id/eprint/86515
DOI: 10.1038/bjc.1994.207

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