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Maintenance of p53 alterations throughout breast cancer progression.

Publication ,  Journal Article
Davidoff, AM; Kerns, BJ; Iglehart, JD; Marks, JR
Published in: Cancer Res
May 15, 1991

Overexpression of the nuclear phosphoprotein p53 is one of the most common abnormalities in primary human cancer and appears to be due to point mutation within a highly conserved region of the p53 gene which then encodes for a mutant, more stable protein. In this study different stages of breast cancer progression were examined, from in situ to metastatic disease, to determine at what stage mutational activation occurs and whether it is maintained during tumor progression. Two (13%) of 15 pure intraductal tumors expressed high levels of p53 in all malignant epithelial cells. Sequencing of p53 mRNA from one of these tumors demonstrated a nucleotide substitution altering the amino acid composition of the protein. Six (17%) of 35 specimens which contained both in situ and invasive disease expressed high levels of p53. All malignant epithelial cells in these 6 cases stained positively and in no specimen did one component express different levels of the protein than the other growth phase. Sequence analysis of a tissue with significant amounts of both in situ and invasive disease revealed only a single point mutation, without evidence of wild-type nucleotide at the site of substitution, suggesting that p53 mRNA from each component of the tumor contained the same nucleotide substitution. Eleven (50%) of 22 pairs of primary tumors and their lymph node metastases expressed elevated levels of p53, and in each case, expression levels were identical in the primary and secondary sites. Identical mutations were found in the p53 mRNA from two paired primary and metastatic sites. Therefore, mutation within a highly conserved region of the p53 gene leading to overexpression of the protein product can occur in the earliest recognized phase of breast cancer and this alteration is maintained during progression from intraductal to infiltrating carcinoma. Mutations are also conserved during the process of metastatic spread.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

May 15, 1991

Volume

51

Issue

10

Start / End Page

2605 / 2610

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • RNA, Neoplasm
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Oligonucleotide Probes
  • Neoplasm Invasiveness
  • Mutation
  • Molecular Sequence Data
  • Immunohistochemistry
  • Humans
 

Citation

APA
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ICMJE
MLA
NLM
Davidoff, A. M., Kerns, B. J., Iglehart, J. D., & Marks, J. R. (1991). Maintenance of p53 alterations throughout breast cancer progression. Cancer Res, 51(10), 2605–2610.
Davidoff, A. M., B. J. Kerns, J. D. Iglehart, and J. R. Marks. “Maintenance of p53 alterations throughout breast cancer progression.Cancer Res 51, no. 10 (May 15, 1991): 2605–10.
Davidoff AM, Kerns BJ, Iglehart JD, Marks JR. Maintenance of p53 alterations throughout breast cancer progression. Cancer Res. 1991 May 15;51(10):2605–10.
Davidoff, A. M., et al. “Maintenance of p53 alterations throughout breast cancer progression.Cancer Res, vol. 51, no. 10, May 1991, pp. 2605–10.
Davidoff AM, Kerns BJ, Iglehart JD, Marks JR. Maintenance of p53 alterations throughout breast cancer progression. Cancer Res. 1991 May 15;51(10):2605–2610.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

May 15, 1991

Volume

51

Issue

10

Start / End Page

2605 / 2610

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • RNA, Neoplasm
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Oligonucleotide Probes
  • Neoplasm Invasiveness
  • Mutation
  • Molecular Sequence Data
  • Immunohistochemistry
  • Humans