Deletion of exons 1a-2 of BRCA1: a rather frequent pathogenic abnormality

Genet Test Mol Biomarkers. 2009 Jun;13(3):399-406. doi: 10.1089/gtmb.2008.0155.

Abstract

Women carrying a pathogenic mutation in either BRCA1 or BRCA2 have a major risk of developing breast and/or ovarian cancer. The majority of mutations in these genes are small point mutations. Since the development of multiplex ligation-dependent probe amplification, an increasing number of large genomic rearrangements have been detected. Here, we describe the characterization of pathogenic deletions of exons 1a-2 of BRCA1 in six families using loss of heterozygosity, array comparative genomic hybridization, and sequence analyses. Two families harbor a 37 kb deletion starting in intron 2 of psi BRCA1, encompassing NBR2, and exons 1a-2 of BRCA1, while the other four families have an 8 kb deletion with breakpoints in intron 2 of NBR2 and intron 2 of BRCA1. This observation, together with the previously described families with exon 1a-2 deletions of BRCA1, demonstrates that this type of deletions is relatively frequent in breast/ovarian cancer families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / genetics
  • Cohort Studies
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • Exons*
  • Family
  • Female
  • Genes, BRCA1*
  • Genetic Markers
  • Haplotypes
  • Humans
  • Introns
  • Loss of Heterozygosity
  • Middle Aged
  • Nucleic Acid Amplification Techniques
  • Nucleic Acid Hybridization
  • Ovarian Neoplasms / genetics
  • Pedigree
  • Point Mutation
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Deletion*

Substances

  • DNA, Neoplasm
  • Genetic Markers