Ann Surg Treat Res.  2017 May;92(5):331-339. 10.4174/astr.2017.92.5.331.

Next-generation sequencing of BRCA1/2 in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results

• Park HS
• Park SJ
• Kim JY
• Kim S
• Ryu J
• Sohn J
• Park S
• Kim GM
• Hwang IS
• Choi JR
• Kim SI

• KMID: 2377703
• DOI: http://doi.org/10.4174/astr.2017.92.5.331

Abstract

PURPOSE
We evaluated the clinical role of rapid next-generation sequencing (NGS) for identifying BRCA1/2 mutations compared to traditional Sanger sequencing.
METHODS
Twenty-four paired samples from 12 patients were analyzed in this prospective study to compare the performance of NGS to the Sanger method. Both NGS and Sanger sequencing were performed in 2 different laboratories using blood samples from patients with breast cancer. We then analyzed the accuracy of NGS in terms of variant calling and determining concordance rates of BRCA1/2 mutation detection.
RESULTS
The overall concordance rate of BRCA1/2 mutation identification was 100%. Variants of unknown significance (VUS) were reported in two cases of BRCA1 and 3 cases of BRCA2 after Sanger sequencing, whereas NGS reported only 1 case of BRCA1 VUS, likely due to differences in reference databases used for mutation identification. The median turnaround time of Sanger sequencing was 22 days (range, 14-26 days), while the median time of NGS was only 6 days (range, 3-21 days).
CONCLUSION
NGS yielded comparably accurate results to Sanger sequencing and in a much shorter time with respect to BRCA1/2 mutation identification. The shorter turnaround time and higher accuracy of NGS may help clinicians make more timely and informed decisions regarding surgery or neoadjuvant chemotherapy in patients with breast cancer.

Keyword

BRCA1; BRCA2; Breast neoplasms; High-throughput nucleotide sequencing

MeSH Terms

Breast Neoplasms*
Breast*
Clinical Decision-Making*
Drug Therapy
High-Throughput Nucleotide Sequencing
Humans
Methods
Prospective Studies

Figure

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  Fig. 1 Study flowchart.

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  Fig. 2 An example of the pedigree charts for a patient with BRCA1 mutation. ca, cancer.

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  Fig. 3 Turnaround time (TAT) between next-generation sequencing (NGS) and Sanger sequencing. The dashed and solid lines indicate TAT of Sanger sequencing and NGS, respectively.

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