Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer

Nat Genet. 1994 Dec;8(4):387-91. doi: 10.1038/ng1294-387.


We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candidate gene, using single-strand conformation polymorphism (SSCP) analysis on PCR-amplified genomic DNA. A total of eight putative disease-causing alterations were identified: four of these are frameshifts and two are nonsense mutations. In addition, we found two missense mutations, one of which changes the final cysteine of the BRCA1 zinc finger motif to glycine. These data are consistent with a tumour suppressor model, and support the notion that this candidate gene is in fact BRCA1. The heterogeneity of mutations, coupled with the large size of the gene, indicates that clinical application of BRCA1 mutation testing will be technically challenging.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age of Onset
  • BRCA1 Protein
  • Base Sequence
  • Breast Neoplasms / genetics*
  • DNA Primers
  • Female
  • Germ-Line Mutation*
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Genetic
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • DNA Primers
  • Neoplasm Proteins
  • Transcription Factors