engleski

New sequence variants in BRCA1 and BRCA2 genes detected by high-resolution melting analysis in an elderly healthy female population in Croatia

Background: Mutations in BRCA1 and BRCA2 genes are associated with family predisposition to breast and ovarian cancer. Novel screening methods are required for efficient and rapid detection of sequence variants in cancer patients and their family members. Methods: The screening for variants in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 in Croatia was performed by a high-resolution melting approach, which is based on differences in melting curves caused by variations in nucleotide sequence. This is the first screening in Croatia on elderly healthy women with no family history of cancer. BRCA1 screening was performed on 220 and BRCA2 on 115 samples. Results: In a population well beyond the average age of breast/ovarian cancer onset, 21 different sequence variants in the BRCA1 gene (one novel: c.5193q49_50delTA) and 36 variants in the BRCA2 gene (7 novel: c.459A)C, c.3318C)A, c.4412_ 4414delGAA, c.4790C)A, c.6264T)C, c.9087G)A, and c.9864A)G) were detected. Conclusions: Nine BRCA1 and seven BRCA2 known variants appeared with such high frequencies that they could be declared as harmless in this population. Eight BRCA1 high frequency variants, located further from the promoter region, appear to be strongly correlated. Three novel variants that changed the amino acid sequence of the BRCA2 protein (two missense base substitutions, c.3318C)A and c.4790C)A, and one codon deletion c.4412_4414delGAA), appearing only once, were predicted to have no potential effect on protein structure and function.

allele frequency; BRCA1; BRCA2; Croatia

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