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Detection of Inherited Mutations for Hereditary Cancer Using Target Enrichment and Next Generation Sequencing

Overview
Journal Fam Cancer
Publisher Springer
Specialty Oncology
Date 2014 Aug 25
PMID 25151137
Citations 15
Authors
Affiliations
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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.

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References
1.
Richards C, Bale S, Bellissimo D, Das S, Grody W, Hegde M . ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med. 2008; 10(4):294-300. DOI: 10.1097/GIM.0b013e31816b5cae. View

2.
Walsh T, Casadei S, Coats K, Swisher E, Stray S, Higgins J . Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006; 295(12):1379-88. DOI: 10.1001/jama.295.12.1379. View

3.
Pritchard C, Smith C, Salipante S, Lee M, Thornton A, Nord A . ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn. 2012; 14(4):357-66. PMC: 3391416. DOI: 10.1016/j.jmoldx.2012.03.002. View

4.
Goossens D, Moens L, Nelis E, Lenaerts A, Glassee W, Kalbe A . Simultaneous mutation and copy number variation (CNV) detection by multiplex PCR-based GS-FLX sequencing. Hum Mutat. 2008; 30(3):472-6. DOI: 10.1002/humu.20873. View

5.
Peltomaki P . Lynch syndrome genes. Fam Cancer. 2005; 4(3):227-32. DOI: 10.1007/s10689-004-7993-0. View