engleski

Polymorphisms of BRCA1 and BRCA2 genes in normal population

Breast cancer is the most frequent malignancy, with 10% of cases attributable to familial inheritance. Hereditary breast cancer is characterised by an inherited susceptibility to breast cancer, which is based on an idenified germline mutation in one allele of a high penetrance susceptibility genes BRCA1 and 2, which are acting as tumor suppressors. They are only genes known to be mutated in familial history of breast cancer. Their main contribution to tumorigenesis is inactivation of the second allele and consequently nonfunctional tumor suppression, which would be an early event in tumorigenic pathway. First step in our study of hereditary breast cancer and inherited susceptibility to breast cancer is to establish a database on BRCA1 and 2 haplotypes in healthy population. Among a wide range of conventional screening methods based on confromational polymorphisms we decided to use procedures based on higr-resolution melting approach. PCR products with fluorescent dye are melted in a High-resolution melter apparatus, giving high-resolution melting curves which show one profile for wild-type samples and a different one if a polymophism or a mutation is present. Result of BRCA1 analysis on over 100 samples of all 24 exons of the gene showed polymorphisms in at least 11 exons. Exons 8, 16 and 17 showed polymorphic patterns in 40-45% of analyzed samples.

BRCA1 ; BRCA2 ; polymorphism ; melting profile

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