Familial Cancer

, Volume 14, Issue 1, pp 9–18 | Cite as

Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing

  • Yanfang Guan
  • Hong Hu
  • Yin Peng
  • Yuhua Gong
  • Yuting Yi
  • Libin Shao
  • Tengfei Liu
  • Gairui Li
  • Rongjiao Wang
  • Pingping Dai
  • Yves-Jean Bignon
  • Zhe Xiao
  • Ling Yang
  • Feng Mu
  • Liang Xiao
  • Zeming Xie
  • Wenhui Yan
  • Nan Xu
  • Dongxian Zhou
  • Xin Yi
Original Article

Abstract

Hereditary cancers occur because of inherited gene mutations. Genetic testing has been approved to provide information for risk assessment and rationale for appropriate intervention. Testing methods currently available for clinical use have some limitations, including sensitivity and testing throughput, etc. Next generation sequencing (NGS) has been rapidly evolving to increase testing sensitivity and throughput. It can be potentially used to identify inherited mutation in clinical diagnostic setting. Here we develop an effective method employing target enrichment and NGS platform to detect common as well as rare mutations for all common hereditary cancers in a single assay. Single base substitution across 115 hereditary cancer related genes using YH (the first Asian genome) was characterized to validate our method. Sensitivity, specificity and accuracy of 93.66, 99.98 and 99.97 %, were achieved, respectively. In addition, we correctly identified 53 SNVs and indels of BRCA1 and BRCA2 in two breast cancer specimens, all confirmed by Sanger sequencing. Accuracy in detecting copy number variation (CNV) was corroborated in 4 breast cancer specimens with known CNVs in BRAC1. Application of the method to 85 clinical cases revealed 22 deleterious mutations, 11 of which were novel. In summary, our studies demonstrate that the target enrichment combined with NGS method provides the accuracy, sensitivity, and high throughput for genetic testing for patients with high risk of hereditary or familial cancer.

Keywords

Genetic testing Hereditary cancer Familial cancer Target enrichment NGS 

Supplementary material

10689_2014_9749_MOESM1_ESM.xls (144 kb)
Supplementary material 1 (XLS 143 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Yanfang Guan
    • 1
    • 2
    • 10
  • Hong Hu
    • 3
  • Yin Peng
    • 2
    • 7
    • 9
  • Yuhua Gong
    • 1
    • 2
    • 10
  • Yuting Yi
    • 1
    • 2
    • 10
  • Libin Shao
    • 2
  • Tengfei Liu
    • 2
  • Gairui Li
    • 2
  • Rongjiao Wang
    • 2
  • Pingping Dai
    • 1
    • 2
    • 10
  • Yves-Jean Bignon
    • 4
    • 5
  • Zhe Xiao
    • 2
  • Ling Yang
    • 1
    • 2
    • 10
  • Feng Mu
    • 2
    • 6
  • Liang Xiao
    • 7
  • Zeming Xie
    • 8
  • Wenhui Yan
    • 3
  • Nan Xu
    • 3
  • Dongxian Zhou
    • 3
  • Xin Yi
    • 1
    • 2
    • 10
  1. 1.Binhai Genomics Institute, BGI-TianjinTianjinChina
  2. 2.BGI-ShenzhenShenzhenChina
  3. 3.Shenzhen People’s HospitalShenzhenChina
  4. 4.Clermont UniversitéClermont-FerrandFrance
  5. 5.Laboratoire d’Oncologie MoléculaireCentre Jean PerrinClermont-FerrandFrance
  6. 6.BGI-BeijingBeijingChina
  7. 7.Shenzhen Second People’s HospitalShenzhenChina
  8. 8.Sun Yat-Sen University Cancer CenterGuangzhouChina
  9. 9.Department of PharmacologySun Yat-Sen UniversityGuangzhouChina
  10. 10.Tianjin Translational Genomics CenterBGI-TianjinTianjinChina

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