Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment
Autor: | Alexander De Jong Robertson, Xin Wang, Diana Jeon, Valentina Vysotskaia, Imran S. Haque, Genevieve Haliburton, Matt Leggett, Lai Henry H, Clement Chu, Gregory J. Hogan, Kevin Iori, Kevin R. Haas, Peter V. Grauman, Genevieve M. Gould, Hyunseok Kang, Mark R. Theilmann, Jared Maguire, Lindsay Spurka, Eric A. Evans, Kaylene Ready |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Analytical validation lcsh:Medicine Alu element Biology Bioinformatics General Biochemistry Genetics and Molecular Biology DNA sequencing 03 medical and health sciences symbols.namesake Germline mutation Next generation sequencing Internal medicine medicine Multiplex Copy-number variation Multiplex ligation-dependent probe amplification Sanger sequencing Multigene panel testing business.industry General Neuroscience lcsh:R Cancer General Medicine Genomics medicine.disease Hereditary cancer 030104 developmental biology symbols General Agricultural and Biological Sciences business Medical Genetics |
Zdroj: | PeerJ, Vol 5, p e3046 (2017) PeerJ |
Popis: | The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy number variants (CNVs) in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers. |
Databáze: | OpenAIRE |
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