Capillary electrophoresis as alternative method to detect tumor genetic mutations: the model built on the founder BRCA1 c.4964_4982del19 variant

Fam Cancer. 2019 Jan;18(1):29-35. doi: 10.1007/s10689-018-0094-2.

Abstract

Despite some populations show a wide spectrum of different BRCA pathogenic variants (PVs), particular ethnic groups carry at high frequency a single or a few recurrent PVs, usually due to a founder effect. The identification of these founder PVs, with simple molecular methods, improves BRCA1/2 testing and cancer risk assessment. In this study, we developed a rapid and reliable PCR method, coupled with capillary electrophoresis (CE) for genotyping the Italian founder BRCA1 c.4964_4982del19 (rs80359876) variant. In addition, we compared the performance of two CE platforms: (Agilent 2100 Bioanalyzer and the Experion Automated Electrophoresis system) to identify this variant. Our findings suggest that CE represents a simple and standardized diagnostic strategy for the unambiguously identification of the BRCA1 c.4964_4982del19 variant, on both germline and somatic DNA samples. The results and performance obtained by two platforms are absolutely superimposable in terms of specificity and sensitivity, as well as for their feasibility, time of analysis and costs.

Keywords: BRCA1/2 genes; Capillary electrophoresis; Italian founder BRCA1/2 mutations.

MeSH terms

  • BRCA1 Protein / genetics*
  • Electrophoresis, Capillary / instrumentation
  • Electrophoresis, Capillary / methods
  • Feasibility Studies
  • Female
  • Founder Effect*
  • Genetic Carrier Screening / instrumentation
  • Genetic Carrier Screening / methods*
  • Genetic Predisposition to Disease*
  • Genotyping Techniques / instrumentation
  • Genotyping Techniques / methods
  • Germ-Line Mutation
  • Humans
  • Italy
  • Loss of Heterozygosity / genetics
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Single Nucleotide
  • Sensitivity and Specificity

Substances

  • BRCA1 Protein
  • BRCA1 protein, human