The variants IVS6-1G>A and IVS15+1G>A lead to aberrant splicing of the transcripts

Sara Gutiérrez-Enríquez (1, 2) , Verònica Coderch (3) , Miriam Masas (1) , Judith Balmaña (4) , Orland Diez (1, 5)

1 Fundació Institut de Recerca de l'Hospital Universitari Vall d'Hebron
2 Laboratori de Biologia Molecular, Laboratoris Clinics
3 Facultat de Biociències
4 Unitat d'Alt Risc i Prevenció del Càncer
5 Programa de Medicina Molecular i Genètica

The majority of and deleterious mutations and variants of unknown significance have been identified in genomic DNA and their effects at the mRNA level have not been reported. Our aim was to ascertain the pathological effect of the IVS6-1G>A (c. 302-1G>A) and the IVS15+1G>A (c. 7617+1G>A) variants detected in Spanish breast/ovarian cancer families. Sequencing of cDNA from the IVS6-1G>A allele revealed an inappropriate splicing of exon 7. The analysis of the IVS15+1G>A allele showed the skipping of exon 15. Both alterations predicted the appearance of premature stop codons. Our findings highlight the importance of studying mutations at DNA and RNA levels in order to clarify the effect of the suspected mutation and to provide adequate counseling for breast/ovarian cancer families.

Mots clés: Hereditary breast cancer; Splicing mutation

Sara Gutiérrez-Enríquez, Verònica Coderch, Miriam Masas, Judith Balmaña, Orland Diez. The variants IVS6-1G>A and IVS15+1G>A lead to aberrant splicing of the transcripts. Breast Cancer Research and Treatment, 2008, 117 (2), pp.461-465. ⟨10.1007/s10549-008-0154-7⟩. ⟨hal-00486595⟩