Characterization of three alternative transcripts of the BRCA1 gene in patients with breast cancer and a family history of breast and/or ovarian cancer who tested negative for pathogenic mutations.

摘要: The study of BRCA1 and BRCA2 genes their alterations has been essential to the understanding development familial breast ovarian cancers. Many variants identified have an unknown pathogenic significance. These include which determine alternative mRNA splicing, in intronic regions those are capable destroying splicing ability. aim this was detect BRCA1/BRCA2 aberrant transcripts resulting from women with a known family history and/or early onset cancer, tested wild-type for BRCA2. identification characterization through analysis levels blood lymphocytes may help us recognize families otherwise misclassified as Blood samples were collected 13 that had cancer negative mutations genes. Total RNA analyzed presence naturally occurring pathological using RT-PCR. In 2 out samples, gene identified. probably they lacked exon 17 15, respectively, giving rise truncated protein. addition these, we Δ17-19 transcript 1 patient, gives protein in-frame deletion 69 amino acids. conclusion, on revealed isoforms (prevalence 15%) pathogenic, not detected by conventional methods mutation screening based direct sequencing all coding regions, intron-exons junctions MLPA analysis.