Mutations in p53 as potential molecular markers for human breast cancer

Ingo B. Runnebaum, Mahalakshmi Nagarajan, Marianne Bowman, Darya Soto, Saraswati Sukumar

Research output: Contribution to journalArticle

Abstract

Based on the high incidence of loss of het-rozgosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern analysis, immunoprecipitation, and nucleotide sequeneing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.

Original languageEnglish (US)
Pages (from-to)10657-10661
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number23
StatePublished - 1991
Externally publishedYes

Fingerprint

p53 Genes
Breast Neoplasms
Mutation
Multiplex Polymerase Chain Reaction
Neoplasms
Breast
Cell Line
Gene Deletion
Mutation Rate
Tumor Suppressor Genes
Oncogenes
Immunoprecipitation
Point Mutation
Exons
Nucleotides
Chromosomes
Messenger RNA
DNA
Incidence
Genes

Keywords

  • Gene mutation
  • Multiplex PCR
  • Protein expression

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Mutations in p53 as potential molecular markers for human breast cancer. / Runnebaum, Ingo B.; Nagarajan, Mahalakshmi; Bowman, Marianne; Soto, Darya; Sukumar, Saraswati.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 23, 1991, p. 10657-10661.

Research output: Contribution to journalArticle

Runnebaum, Ingo B. ; Nagarajan, Mahalakshmi ; Bowman, Marianne ; Soto, Darya ; Sukumar, Saraswati. / Mutations in p53 as potential molecular markers for human breast cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 23. pp. 10657-10661.
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