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Anticancer Res. 1993 Sep-Oct;13(5A):1619-23.

p53 gene mutation spectrum in human unknown primary tumors.

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Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.


Mutations affecting the p53 gene are associated with many human malignancies, but little is known about changes in p53 in unknown primary tumors (UPTs), which are characterized as tumors with advanced stages of malignancy. We therefore investigated the frequency of p53 mutations in a series of 15 unknown primary tumor biopsies and eight cell lines established from UPTs. Mutations in the conserved regions of the p53 gene were verified by single-strand conformation polymorphism analysis of exons 5-9 and were verified by direct DNA sequencing of polymerase chain reaction products. A point mutation leading to an amino acid change in the p53 protein was found in six cases, and a mutation causing a change to termination was found in one case. A frameshift mutation was observed in one cell line. In one patient and one cell line we observed more than one mutation in the p53 coding sequence. Overall, the frequency of mutations that changed the p53 coding sequence in the UPTs we studied was 26% (6/23). Mutations were distributed in eight codons of the p53 gene. Seven of these tumors showed a reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. We conclude that although UPTs represent highly metastatic advanced tumors that are expected to have a high incidence of p53 mutations, the frequency of p53 mutations is relatively low, suggesting that p53 mutations may not play a major role in the development and progression of this unique tumor type.

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