Genetic basis for p53 overexpression in human breast cancer.

Journal Article

Overexpression of an activated form of the p53 protein may be involved in neoplastic transformation. We found widespread overexpression of p53 by immunohistochemical staining in 11 (22%) of 49 primary invasive human breast cancers. Northern blot analysis showed that this overexpression was not due to an increase in the steady-state level of p53 mRNA. The p53 gene was directly sequenced in 7 of these tumors with elevated levels of the protein and, in each case, a mutation that altered the coding sequence for p53 was found in a highly conserved region of the gene. Whereas 4 of these tumors contained only a mutant p53 allele, the other 3 tumors exhibited coding sequences from both a mutant and a wild-type allele. p53 mutations have previously been correlated with allelic loss of part of chromosome 17p that contains the p53 locus. Examination of all 49 breast tumors revealed a 61% frequency of deletion at or near the p53 locus. However, the presence of allelic deletion did not correlate with overexpression of the protein. Six tumors that were deleted but did not express high levels of the protein were sequenced and all retained a wild-type p53 allele. In this series of human breast cancers, overexpression of the p53 protein, not allelic loss on chromosome 17p, was always associated with mutation of the p53 gene.

Full Text

Duke Authors

Cited Authors

  • Davidoff, AM; Humphrey, PA; Iglehart, JD; Marks, JR

Published Date

  • June 1, 1991

Published In

Volume / Issue

  • 88 / 11

Start / End Page

  • 5006 - 5010

PubMed ID

  • 2052583

International Standard Serial Number (ISSN)

  • 0027-8424

Language

  • eng

Conference Location

  • United States