Somatic BRCA1 and BRCA2 detection in homologous recombination deficiency testing: concordance of four sequencing workflows with the Myriad myChoice companion diagnostic.

In 30 seconds

This multicenter study assessed agreement between four tumor sequencing workflows and the Myriad myChoice companion diagnostic for BRCA1/BRCA2 variant detection in newly diagnosed ovarian cancer. Of 100 formalin-fixed, paraffin-embedded samples, 98 were evaluable after two failed reference tests. All four workflows and myChoice agreed completely in 86 of 98 samples (87.8%). The 12 discordant cases reflected technical or interpretive differences, including copy-number detection, low-frequency variants, variant-of-uncertain-significance reporting, and transcript or nomenclature inconsistencies. No workflow showed systematic over-calling or under-calling.

Key findings

• Complete agreement across all four workflows and myChoice occurred in 86 of 98 evaluable samples (87.8%).
• Discordance affected 12 of 98 cases (12.2%) and arose from four recurring technical or interpretive categories.
• No sequencing workflow showed systematic over-calling or under-calling relative to the reference assay.

Why it matters

BRCA1/BRCA2 results can inform treatment decisions and referral for hereditary cancer assessment. The observed cross-platform differences show that assay and interpretation choices may affect whether results align across testing workflows, underscoring the value of consistent methods and reporting for reliable clinical communication.

What to keep in mind

Two samples failed reference testing and were excluded; the study assessed agreement with one reference assay rather than clinical outcomes.