Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 May;92(5):331-339.
doi: 10.4174/astr.2017.92.5.331. Epub 2017 Apr 27.

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

Hyung Seok Park  1 , Seo-Jin Park  2 , Jee Ye Kim  1 , Sanghwa Kim  1 , Jaegyu Ryu  1 , Joohyuk Sohn  3 , Seho Park  1 , Gun Min Kim  3 , In Sik Hwang  4 , Jong-Rak Choi  2   4 , Seung Il Kim  1
Affiliations

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

Hyung Seok Park et al. Ann Surg Treat Res. 2017 May.

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.

Keywords: BRCA1; BRCA2; Breast neoplasms; High-throughput nucleotide sequencing.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1. Study flowchart.
Fig. 2
Fig. 2. An example of the pedigree charts for a patient with BRCA1 mutation. ca, cancer.
Fig. 3
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.
See this image and copyright information in PMC

References

    1. King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–646. - PubMed
    1. Schenberg T, Mitchell G. Prophylactic bilateral salpingectomy as a prevention strategy in women at high-risk of ovarian cancer: a mini-review. Front Oncol. 2014;4:21. - PMC - PubMed
    1. Wevers MR, Aaronson NK, Verhoef S, Bleiker EM, Hahn DE, Kuenen MA, et al. Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial. Br J Cancer. 2014;110:1081–1087. - PMC - PubMed
    1. Evans DG, Lalloo F, Ashcroft L, Shenton A, Clancy T, Baildam AD, et al. Uptake of risk-reducing surgery in unaffected women at high risk of breast and ovarian cancer is risk, age, and time dependent. Cancer Epidemiol Biomarkers Prev. 2009;18:2318–2324. - PubMed
    1. Schwartz MD, Lerman C, Brogan B, Peshkin BN, Halbert CH, DeMarco T, et al. Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J Clin Oncol. 2004;22:1823–1829. - PubMed

LinkOut - more resources