Next-generation sequencing of BRCA1/2 in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results.
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.
['Park|Hyung Seok|HS|', 'Park|Seo-Jin|SJ|', 'Kim|Jee Ye|JY|', 'Kim|Sanghwa|S|', 'Ryu|Jaegyu|J|', 'Sohn|Joohyuk|J|', 'Park|Seho|S|', 'Kim|Gun Min|GM|', 'Hwang|In Sik|IS|', 'Choi|Jong-Rak|JR|', 'Kim|Seung Il|SI|']
BRCA1 BRCA2 Breast neoplasms High-throughput nucleotide sequencing