Screening for mutations in exon 11 of the BRCA1 gene in 70 Italian breast and ovarian cancer patients by protein truncation test

Oncogene. 1996 Sep 19;13(6):1353-7.

Abstract

The most common mutations in the familial breast and ovarian cancer susceptibility gene BRCA1 are frameshift and nonsense mutations, which lead to the synthesis of truncated proteins. On this ground, we have analysed BRCA1 exon 11, which includes about 61% of coding region, in germline DNA from 70 Italian breast and/or ovarian cancer patients, using the protein truncation test (PTT). BRCA1 mutations were identified in nine of 29 (approximately 31%) patients with a family history of cancer and in three of 41 (approximately 7%) women with early-onset breast carcinomas, and were subsequently characterized by sequence analysis. In addition, BRCA1 mutations were also detected in six affected relatives of two positive index cases. The observed frequencies of mutations were not significantly different from those expected on the basis of the phenotypic characteristics of patients and their families, indicating that PTT is a rapid and sensitive method that can be used for a first BRCA1 mutational screening. The histological findings in BRCA1 mutated cases showed that eight of nine (approximately 89%) breast carcinomas were of grade III and nine of 9 (100%) ovarian carcinomas were of the endometrioid type (eight of grade III and one of grade II). This suggests that specific histological characteristics may represent additional criteria for selection of cases eligible to BRCA1 mutational analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BRCA1 Protein / analysis
  • BRCA1 Protein / genetics*
  • Breast Neoplasms / genetics*
  • DNA, Neoplasm / genetics
  • Exons*
  • Female
  • Genetic Markers
  • Genetic Testing
  • Humans
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Phenotype
  • Sensitivity and Specificity

Substances

  • BRCA1 Protein
  • DNA, Neoplasm
  • Genetic Markers
  • Neoplasm Proteins