engleski

Physiological significance of polymorphisms in BRCA1 and BRCA2. Difference in melting profile reflecting polymorphic or mutational variability

Breast cancer is the most frequent malignancy with 10% attributable to familial inheritance. Hereditary breast cancer is characterised by an inherited susceptibility to breast cancer. The main candidates are BRCA1 and 2 genes, which are acting as tumor suppressors, and are only genes known to be mutated in familial history of breast cancer. In familial cases an individal already ccarries a mutation in one of the alleles. Tumorigenesis is a result of inactivation of the second allele. We are analyzing distribution of polymorphisms of BRCA1 and 2 genes in normal population to establish the reference values in healthy population, since no such screening has been undertaken. We are evaluating polymorphic forms of BRCA1 and 2 as a mean to eliminate variants with no clear mutational value often found in patients. The data we collect will be used as reference in determining mutations in patients. Among a wide range of conventional mutation scanning mathods based on conformational polymorphisms we decided to use the procedures based on high resoultion melting approach. We used High resolution melting apparatus (Idaho Technology) in combination with adapted Rapid Cycler (and fluorescent dye) to detect polymorphisms which are distinguished from the wild-type genotype by changes in melting curve shape or position. This analysis contributes to the program of an early detection and prevention of breast cancer in Croatia.

BRCA1 ; BRCA2 ; polymorphism ; melting profile

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