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Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

BRCA1 and BRCA2 (BRCA1/2) are two major high-penetrance breast cancer predisposition genes, mutations in which can lead to high risks and early onset of breast cancer. This study was performed to comprehensively investigate the spectrum and prevalence of BRCA1/2 mutations in unselected Chinese breast cancer patients and evaluate the associations of BRCA1/2 mutations with related clinicopathological characteristics of the tumors.

Methods

By integrating microfluidic PCR-based target enrichment and next-generation sequencing, paired tumor and normal tissues from 313 unselected breast cancer patients were analyzed for both germline and somatic mutations of BRCA1/2 genes in Chinese Han population.

Results

Total 5 BRCA1 and 8 BRCA2 deleterious germline mutations were detected in 5 (1.60%) and 12 (3.83%) of the 313 patients, respectively. The entire frequency of deleterious germline mutations of BRCA1/2 was 5.43%. Among them, c.1069A > T and c.3418_3419insTGACTACT in BRCA1, c.8474_8487delCATACCCTATACAG and c.6547delG in BRCA2 were novel. In addition, 32 germline variants of unknown significance in 31 (9.90%) of the 313 patients were identified. We also detected 13 somatic mutations in ten patients (3.19%), including 4 (1.28%) deleterious mutations (c.1575delT, c.2677C > T, c.7024C > T, and c.7672G > T in BRCA2) and 5 novel mutations (c.4728A > G and c.4820T > C in BRCA1; c.2527G > A, c.4069C > G and c.7672G > T in BRCA2). Notably, BRCA1 mutation carriers were significantly younger, and more likely to be ER negative and basal-like breast cancers.

Conclusions

Our study provided a reliable and effective platform for BRCA1/2 genetic testing, and suggested that there was a relatively high prevalence and special spectrum of BRCA1/2 mutations in unselected Chinese breast cancer patients.

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Abbreviations

ER:

Estrogen receptor

PR:

Progesterone receptor

HER2:

Human epidermal growth factor receptor-2

IFC:

Integrated fluidic circuit

NGS:

Next-generation sequencing

PARP:

Poly ADP-ribose polymerase

SNV:

Single-nucleotide variant

VUS:

Variants of unknown significance

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Acknowledgements

This work was supported in part by grants from the Natural Science Foundation of China (No. 81372228), and grants from China Hunan Provincial Science and Technology Department (No. 2016GK3022, 2016XK2033, and 2016JC2068).

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Authors and Affiliations

  1. The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, China

    Guoli Li & Jun Wang

  2. Sanway Gene Technology Inc., Changsha, Hunan, 410205, China

    Xinwu Guo, Ming Chen, Xipeng Luo, Limin Peng, Xunxun Xu & Lizhong Dai

  3. Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Lili Tang, Shouman Wang & Zhi Xiao

  4. Department of Breast and Thyroid Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Wenjun Yi

  5. Research Center for Technologies in Nucleic Acid-Based Diagnostics, Changsha, Hunan, 410205, China

    Lizhong Dai

  6. Research Center for Technologies in Nucleic Acid-Based Diagnostics and Therapeutics, Changsha, Hunan, 410205, China

    Lizhong Dai

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  1. Guoli Li
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  2. Xinwu Guo
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Correspondence to Jun Wang.

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We declare that the experiments performed in this study comply with the current laws of the People’s Republic of China.

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Xinwu Guo, Ming Chen, Xipeng Luo, Limin Peng, Xunxun Xu, and Lizhong Dai are employees of Sanway Gene Technology Inc.

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Li, G., Guo, X., Tang, L. et al. Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing. J Cancer Res Clin Oncol 143, 2011–2024 (2017). https://doi.org/10.1007/s00432-017-2465-8

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