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. 2016 Jun 28:4:e2162.
doi: 10.7717/peerj.2162. eCollection 2016.

Design and validation of a next generation sequencing assay for hereditary BRCA1 and BRCA2 mutation testing

Hyunseok P Kang  1 , Jared R Maguire  1 , Clement S Chu  1 , Imran S Haque  1 , Henry Lai  1 , Rebecca Mar-Heyming  1 , Kaylene Ready  1 , Valentina S Vysotskaia  1 , Eric A Evans  1
Affiliations

Design and validation of a next generation sequencing assay for hereditary BRCA1 and BRCA2 mutation testing

Hyunseok P Kang et al. PeerJ. .

Abstract

Hereditary breast and ovarian cancer syndrome, caused by a germline pathogenic variant in the BRCA1 or BRCA2 (BRCA1/2) genes, is characterized by an increased risk for breast, ovarian, pancreatic and other cancers. Identification of those who have a BRCA1/2 mutation is important so that they can take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. We describe the design and analytic validation of the Counsyl Inherited Cancer Screen, a next-generation-sequencing-based test to detect pathogenic variation in the BRCA1 and BRCA2 genes. We demonstrate that the test is capable of detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy-number variants (CNVs, also known as large rearrangements) with zero errors over a 114-sample validation set consisting of samples from cell lines and deidentified patient samples, including 36 samples with BRCA1/2pathogenic germline mutations.

Keywords: Analytical validation; BRCA testing; Hereditary breast and ovarian cancer; Next generation sequencing assay.

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Conflict of interest statement

All authors are employees and shareholders of Counsyl Inc., and the manuscript describes the validation of a commercial genetic test.

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References

    1. Alsop K, Fereday S, Meldrum C, DeFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, Friedlander M, Fox S, Bowtell D, Mitchell G. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. Journal of Clinical Oncology. 2012;30(21):2654–2663. doi: 10.1200/JCO.2011.39.8545. - DOI - PMC - PubMed
    1. American College of Medical Genetics and Genomics 2015. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Available at https://www.acmg.net/ (accessed 27 February 2015)
    1. American Society of Human Genetics Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. American Journal of Human Genetics. 1994;55(5):i–iv. - PMC - PubMed
    1. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjäkoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. American Journal of Human Genetics. 2003;72(5):1117–1130. doi: 10.1086/375033. - DOI - PMC - PubMed
    1. Balmaña J, Díez O, Rubio IT, Cardoso F. BRCA in breast cancer: ESAMO clinical practice guidelines. Annals of Oncology. 2011;22(Suppl 6):vi31–vi34. doi: 10.1093/annonc/mdr373. - DOI - PubMed