Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on...

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Veröffentlicht in:Scientific reports Jg. 9; H. 1; S. 17052 - 16
Hauptverfasser: McCabe, Mark J., Gauthier, Marie-Emilie A., Chan, Chia-Ling, Thompson, Tanya J., De Sousa, Sunita M.C., Puttick, Clare, Grady, John P., Gayevskiy, Velimir, Tao, Jiang, Ying, Kevin, Cipponi, Arcadi, Deng, Niantao, Swarbrick, Alex, Thomas, Melissa L., Lord, Reginald V., Johns, Amber L., Kohonen-Corish, Maija, O’Toole, Sandra A., Clark, Jonathan, Mueller, Simon A., Gupta, Ruta, McCormack, Ann I., Dinger, Marcel E., Cowley, Mark J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 19.11.2019
Nature Publishing Group
Schlagworte:
45/23
45/41
45/47
631/208/514/2254
631/67/69
692/4028/67/69
Bioinformatics
Biomarkers, Tumor - genetics
Biopsy
Cancer
Carcinoma, Pancreatic Ductal - genetics
Cell Line, Tumor
Circulating Tumor DNA - genetics
Computational Biology - methods
Deoxyribonucleic acid
DNA
DNA sequencing
Gene frequency
Genetic Predisposition to Disease - genetics
Genetic testing
Genomics - methods
Head & neck cancer
Head and Neck Neoplasms - genetics
High-Throughput Nucleotide Sequencing - methods
Humanities and Social Sciences
Humans
Liquid Biopsy
multidisciplinary
Next-generation sequencing
Oncology
Pancreatic Neoplasms - genetics
Pituitary Neoplasms - genetics
Precision medicine
Precision Medicine - methods
Science
Science (multidisciplinary)
Sensitivity and Specificity
Squamous Cell Carcinoma of Head and Neck - genetics
Tumors
ISSN:2045-2322, 2045-2322
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Zusammenfassung:Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein ( AIP ) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-52000-3