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

Mark J. McCabe, Marie-Emilie A. Gauthier, Chia-Ling Chan, Tanya J. Thompson, Sunita M. C. De Sousa, Clare Puttick, John P. Grady, Velimir Gayevskiy, Jiang Tao, Kevin Ying, Arcadi Cipponi, Niantao Deng, Alex Swarbrick, Melissa L. Thomas, Morteza Aghmesheh, David Amor, Lesley Andrews, Yoland Antill, Shane Armitage, Leanne ArnoldRosemary Balleine, Patti Bastik, Jonathan Beesley, John Beilby, Ian Bennett, Anneke Blackburn, Michael Bogwitz, Leon Botes, Meagan Brennan, Melissa Brown, Michael Buckley, Matthew J. Burgess, Jo Burke, Phyllis Butow, Liz Caldon, David Callen, Ian Campbell, Deepa Chauhan, Manisha Chauhan, Georgia Chenevix-Trench, Alice Christian, Christine Clarke, Paul Cohen, Alison Colley, Ashley Crook, James Cui, Bronwyn Culling, Margaret Cummings, Sarah-Jane Dawson, Anna deFazio, Martin Delatycki, Rebecca Dickson, Joanne Dixon, Alexander Dobrovic, Tracy Dudding, Ted Edkins, Stacey Edwards, Maurice Eisenbruch, Gelareh Farshid, Andrew Fellows, Georgina Fenton, Michael Field, James Flanagan, Peter Fong, Laura Forrest, Stephen Fox, Juliet French, Michael Friedlander, Clara Gaff, David Gallego, Mike Gatta, Peter George, Graham Giles, Grantley Gill, Sian Greening, Eric Haan, Marion Harris, Stewart Hart, Nick Hayward, Louise Heiniger, John Hopper, Clare Hunt, Paul James, Mark Jenkins, Rick Kefford, Alexa Kidd, Judy Kirk, Jessica Koehler, James Kollias, Sunil Lakhini, Geoff Lindeman, Lara Lipton, Liz Lobb, Graham Mann, Deborah Marsh, Sue Ann McLachaln, Bettina Meiser, Roger Milne, Sophie Nightingale, Shona O'Connell, Sarah O'Sullivan, Nick Pachter, Briony Patterson, Kelly Phillips, Ellen Pieper, Edwina Rickard, Bridget Robinson, Mona Saleh, Elizabeth Salisbury, Joe Sambrook, Christobel Saunders, Jodi Saunus, Elizabeth Salisbury, Clare L. Scott, Rodney Scott, Adrienne Sexton, Andrew Shelling, Peter Simpson, Melissa Southey, Amanda Spurdle, Jessica Taylor, Heather Thorne, Alison Trainer, Kathy Tucker, Jane Visvader, Logan Walker, Rachael Williams, Ingrid Winship, Mary-Anne Young, Reginald V. Lord, Amber L. Johns, Maija Kohonen-Corish, Sandra A. O'Toole, et al

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article number17052
Number of pages16
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019

Open Access - Access Right Statement

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Keywords

  • cancer
  • exomes
  • genes
  • genomes

Fingerprint

Dive into the research topics of 'Development and validation of a targeted gene sequencing panel for application to disparate cancers'. Together they form a unique fingerprint.

Cite this