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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Vydané v:	Scientific reports Ročník 9; číslo 1; s. 17052 - 16
Hlavní autori:	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.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 19.11.2019 Nature Publishing Group
Predmet:	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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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-019-52000-3