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p53 mutations in breast cancer.

C Coles1, A Condie, U Chetty

  • 1MRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland.

Cancer Research
|October 1, 1992
PubMed
Summary

Approximately 40% of sporadic breast tumors harbor p53 mutations, with a higher than expected frequency of G-T transversions suggesting a role for exogenous carcinogens in breast cancer development.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The p53 tumor suppressor gene plays a critical role in preventing cancer.
  • Mutations in p53 are common in many human cancers, but their specific role in sporadic breast cancer requires further investigation.

Purpose of the Study:

  • To identify and analyze p53 gene mutations in sporadic breast tumors.
  • To determine the frequency and spectrum of p53 mutations in a cohort of unselected breast cancer patients.
  • To explore the potential etiological factors, including exogenous carcinogens and germ-line mutations, contributing to sporadic breast cancer.

Main Methods:

  • Analysis of 41 mutations in the p53 gene from 136 unselected sporadic breast tumor samples.
  • Statistical analysis to determine mutation frequency, distribution across codons, and types of mutations.
  • Assessment of germ-line p53 mutations in the patient cohort.

Main Results:

  • Approximately 40% of sporadic breast tumors analyzed contained p53 mutations.
  • A higher than expected frequency of G-T transversions and guanosine mutations in the nontranscribed strand of the p53 gene was observed.
  • Mutations were distributed across 44 codons, with no distinct mutational hotspots, although codons 175, 194, 273, and 280 accounted for 25% of mutations.
  • Only one germ-line p53 mutation was identified among the 136 patients.

Conclusions:

  • The findings suggest that exogenous carcinogens may play a significant etiological role in the development of sporadic breast cancer.
  • Constitutional p53 mutation appears to be an uncommon factor in the etiology of sporadic breast cancer.

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