1. RNA-based analysis of BRCA1 and BRCA2 gene alterations
- Author
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Elisa Sensi, Generoso Bevilacqua, G Cipollini, Paolo Aretini, Grazia Lombardi, Maria A. Caligo, Fabrizia Bonatti, Mariella Tancredi, Chiara Pepe, and Elisabetta Falaschi
- Subjects
Male ,Cancer Research ,endocrine system diseases ,RNA Splicing ,DNA Mutational Analysis ,Genes, BRCA2 ,Genes, BRCA1 ,Breast Neoplasms ,Biology ,Frameshift mutation ,Exon ,Germline mutation ,Genetics ,Humans ,RNA, Messenger ,skin and connective tissue diseases ,neoplasms ,Molecular Biology ,Gene ,Germ-Line Mutation ,Ovarian Neoplasms ,Messenger RNA ,Base Sequence ,Alternative splicing ,RNA ,Sequence Analysis, DNA ,female genital diseases and pregnancy complications ,Pedigree ,Alternative Splicing ,RNA splicing ,Female ,RNA Splice Sites ,Software - Abstract
Alterations in BRCA1 and BRCA2 genes account for a large proportion of hereditary breast and ovarian cancers. Mutations and variants of unknown pathological significance have been identified in both genes; however, most of them have been studied only at the genomic level, and their effect on mRNA expression remains unknown. We identified two BRCA1 and six BRCA2 splice site variants, and one BRCA2 alteration at exon 14. Our aim was to ascertain the effect on RNA processing of the variants still unclassified. We found that BRCA1 c.IVS11 + 1G>A, BRCA2 c.7252_7272delinsTG, BRCA2 c.IVS2 + 1G>A, BRCA2 c.IVS13-2A>G, BRCA2 c.IVS21 + 4A>G, and BRCA2 c.9345G>A lead to aberrant transcripts in lymphocytes. Five of these six splice site variants caused a complete inactivation of the mutant allele because they produced frameshift similar to previously described deleterious exonic variants. Therefore, we consider them to be true deleterious mutations, possibly associated with an increased lifetime risk of breast or ovarian cancer. BRCA1 c.IVS17 + 6C>G, BRCA2 c.IVS12-9del4, and BRCA2 IVS1-9del3 represent rare variants, not disrupting normal mRNA processing. The last two BRCA2 genetic variants had not been reported in the Breast Cancer Information Core BIC database.
- Published
- 2006