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

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 Department of Genetics
2 Department of Medical Oncology
3 Department of Surgical Oncology
4 Institute of Molecular Pathology and Immunology
5 Faculty of Sciences
6 Institute of Biomedical Sciences (ICBAS)

We evaluated the contribution of an Alu insertion in 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 mutation in 14 families and showed that it accounts for more that one-fourth of deleterious / mutations in breast/ovarian cancer families originated from this part of the country. This mutation originates exon 3 skipping and we demonstrated its pathogenic effect by showing that the 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 differed from that observed in the other two. Although the c.156_157insAlu 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.

Mots clés: c.156_157insAlu mutation; Breast cancer; Hereditary predisposition

Ana Peixoto, Catarina Santos, Patrícia Rocha, Manuela Pinheiro, Sofia Príncipe, et al.. The c.156_157insAlu rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal. Breast Cancer Research and Treatment, 2008, 114 (1), pp.31-38. ⟨10.1007/s10549-008-9978-4⟩. ⟨hal-00478331⟩