Abstract
Introduction
Detection of pathogenic variants in hereditary breast and ovarian cancer-related breast cancer type 1 and type 2 susceptibility proteins (BRCA1/2) genes is an effective strategy in cancer prevention and treatment. Some ethnic and geographical regions show different BRCA1/2 mutation spectrum and prevalence. In Italy, elucidation of founder effect in BRCA1/2 genes can have an impact on the management of hereditary cancer families on a healthcare system level, making genetic testing more affordable and cost effective in certain regions.
Methods
The purpose of this paper is to develop a rapid, low-cost, high-throughput single-tube technology for genotyping the Italian founder mutation c.4964_4982del19 (rs80359876) in the BRCA1 gene, starting from peripheral blood and/or buccal swab DNA.
Results
Heterozygote samples for c.4964_4982del19 variant were easily and unambiguously identified by the altered shape of the melting curves and were clearly distinguished by a change in melting temperature that differed by approximately 5 °C. The same results were obtained both with DNA from peripheral blood than buccal swab.
Conclusions
We provide evidence about application of high-resolution melting analysis (HRMA) in unambiguously genotyping of the founder BRCA1 c.4964_4982del19 variant (rs80359876) in individuals from the Calabria region of Italy. In fact, HRMA was confirmed to be particularly suitable for the identification of BRCA1 c.4964_4982del19 variant, making this approach useful in clinical molecular diagnostics.
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The authors (AM, MDB, EDP, LG, CS, PC, FM and EC) declare they have no competing interests.
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The study was performed ensuring compliance of human studies with the Helsinki Declaration.
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An erratum to this article is available at http://dx.doi.org/10.1007/s40291-017-0273-0.
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Minucci, A., De Bonis, M., De Paolis, E. et al. High Resolution Melting Analysis is Very Useful to Identify Breast Cancer Type 1 Susceptibility Protein (BRCA1) c.4964_4982del19 (rs80359876) Founder Calabrian Pathogenic Variant on Peripheral Blood and Buccal Swab DNA. Mol Diagn Ther 21, 217–223 (2017). https://doi.org/10.1007/s40291-017-0262-3
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DOI: https://doi.org/10.1007/s40291-017-0262-3