Breast Cancer Research and Treatment

, Volume 114, Issue 1, pp 31–38 | Cite as

The c.156_157insAlu BRCA2 rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal

  • Ana Peixoto
  • Catarina Santos
  • Patrícia Rocha
  • Manuela Pinheiro
  • Sofia Príncipe
  • Deolinda Pereira
  • Helena Rodrigues
  • Fernando Castro
  • Joaquim Abreu
  • Leonor Gusmão
  • António Amorim
  • Manuel R. Teixeira
Preclinical Study

Abstract

We evaluated the contribution of an Alu insertion in BRCA2 exon 3 (c.156_157insAlu) to inherited predisposition to breast/ovarian cancer in 208 families originated mostly from northern/central Portugal. We identified the c.156_157insAlu BRCA2 mutation in 14 families and showed that it accounts for more that one-fourth of deleterious BRCA1/BRCA2 mutations in breast/ovarian cancer families originated from this part of the country. This mutation originates BRCA2 exon 3 skipping and we demonstrated its pathogenic effect by showing that the BRCA2 full length transcript is derived only from the wild type allele in carriers, that it is absent in 262 chromosomes from healthy blood donors, and that it co-segregates with the disease. Polymorphic microsatellite markers were used for haplotype analysis in three informative families. In two of the three families one haplotype was shared for all but two markers, whereas in the third family all markers telomeric to BRCA2 differed from that observed in the other two. Although the c.156_157insAlu BRCA2 mutation has so far only been identified in Portuguese breast/ovarian cancer families, screening of this rearrangement in other populations will allow evaluation of whether or not it is a population-specific founder mutation and a more accurate estimation of its distribution and age.

Keywords

c.156_157insAlu BRCA2 mutation Breast cancer Hereditary predisposition 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Ana Peixoto
    • 1
  • Catarina Santos
    • 1
  • Patrícia Rocha
    • 1
  • Manuela Pinheiro
    • 1
  • Sofia Príncipe
    • 1
  • Deolinda Pereira
    • 2
  • Helena Rodrigues
    • 2
  • Fernando Castro
    • 3
  • Joaquim Abreu
    • 3
  • Leonor Gusmão
    • 4
  • António Amorim
    • 4
    • 5
  • Manuel R. Teixeira
    • 1
    • 6
  1. 1.Department of GeneticsPortuguese Oncology InstitutePortoPortugal
  2. 2.Department of Medical OncologyPortuguese Oncology InstitutePortoPortugal
  3. 3.Department of Surgical OncologyPortuguese Oncology InstitutePortoPortugal
  4. 4.Institute of Molecular Pathology and ImmunologyUniversity of Porto (IPATIMUP)PortoPortugal
  5. 5.Faculty of SciencesUniversity of PortoPortoPortugal
  6. 6.Institute of Biomedical Sciences (ICBAS)University of PortoPortoPortugal

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