title: Design and validation of a next generation sequencing assay for hereditary BRCA1 and BRCA2 mutation testing.
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.
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Hyunseok P
authors.initials: HP
authors.lastname: Kang
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Jared R
authors.initials: JR
authors.lastname: Maguire
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Clement S
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Imran S
authors.initials: IS
authors.lastname: Haque
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Henry
authors.initials: H
authors.lastname: Lai
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mar-Heyming
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Kaylene
authors.initials: K
authors.lastname: Ready
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Valentina S
authors.initials: VS
authors.lastname: Vysotskaia
authors.affiliation: Counsyl Inc. , South San Francisco , CA , United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Evans
keywords: Analytical validation; BRCA testing; Hereditary breast and ovarian cancer; Next generation sequencing assay