The majority of BRCA1 and BRCA2 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 BRCA1 IVS6-1G>A (c. 302-1G>A) and the BRCA2 IVS15+1G>A (c. 7617+1G>A) variants detected in Spanish breast/ovarian cancer families. Sequencing of cDNA from the BRCA1 IVS6-1G>A allele revealed an inappropriate splicing of exon 7. The analysis of the BRCA2 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10549-008-0154-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The variants BRCA1 IVS6-1G>A and BRCA2 IVS15+1G>A lead to aberrant splicing of the transcripts.
Breast Cancer Res Treat
September 2009
Fundació Institut de Recerca de l'Hospital Universitari Vall d'Hebron, Barcelona, Spain.
The majority of BRCA1 and BRCA2 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 BRCA1 IVS6-1G>A (c. 302-1G>A) and the BRCA2 IVS15+1G>A (c.
View Article and Find Full Text PDFBRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families.
Br J Cancer
March 2004
Centre for Medical Genetics, Ghent University Hospital, De Pintelaan 185, Gent 9000, Belgium.
Worldwide variation in the distribution of BRCA1 and BRCA2 mutations is well recognised, and for the Belgian population no comprehensive studies about BRCA1/2 mutation spectra or frequencies have been published. We screened the complete coding region of both genes in 451 individuals from 349 Belgian families referred to a family cancer clinic and identified 49 families with a BRCA1 and 26 families with a BRCA2 mutation. Six major recurrent mutations (BRCA1 IVS5+3A>G, 2478-2479insG, E1221X and BRCA2 IVS6+1G>A, 6503-6504delTT, 9132delC) accounted for nearly 60% of all mutations identified.
View Article and Find Full Text PDFDifferentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2.
Genes Chromosomes Cancer
July 2003
Center for Medical Genetics, Ghent University Hospital, Belgium.
About 4% of all BRCA1 and BRCA2 alterations reported to the Breast Information Core database are splice site variants. Only a limited number of them have been studied at the RNA level. By BRCA1 and BRCA2 mutation analysis of breast/ovarian cancer families, we identified two novel and eight previously reported potential splice site mutations, never characterized at the cDNA level before.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!