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

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.

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Abbreviations

HBOCS:

Hereditary breast and ovarian carcinoma syndrome

PVs:

Pathogenic variants

iPARP-1:

Poly(ADP-ribose) polymerase 1-inhibitors

HGSC:

High-grade serous carcinoma

NGS:

Next generation sequencing

CE:

Capillary electrophoresis

FFPE:

Formalin fixed paraffin embedded

LOH:

Loss of heterozygosis

MPS:

Massively parallel sequencing

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Correspondence to Ettore Capoluongo.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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De Bonis, M., Minucci, A., Scaglione, G.L. et al. Capillary electrophoresis as alternative method to detect tumor genetic mutations: the model built on the founder BRCA1 c.4964_4982del19 variant. Familial Cancer 18, 29–35 (2019). https://doi.org/10.1007/s10689-018-0094-2

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Keywords

  • BRCA1/2 genes
  • Capillary electrophoresis
  • Italian founder BRCA1/2 mutations