1. Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue
- Author
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Richard Marais, Andrew Furness, Thomas B.K. Watkins, Maise Al-Bakir, Dionysis Papadatos-Pastos, Maryam Razaq, Mairead McKenzie, Lisa Pickering, Peter Ellery, Jonathan Ledermann, Andrew V. Biankin, Richard J. Gilbertson, Peter Cockcroft, Mary Mangwende, Sophie Ward, Mary Falzon, Cristina Naceur-Lombardelli, Carlos Caldas, Karla Pearce, Jacqui Shaw, Salma Kadiri, Lars Dyrskjøt, Mark Linch, Daniel Burgess, Nelson Alexander, Christian H. Ottensmeier, Kevin G. Blyth, Lisa L. Gallegos, Rodelaine Wilson, Hayley Bridger, Fiona H Blackhall, Peter J. Parker, Charles Swanton, Allan Hackshaw, Gert Attard, Gordon Stamp, Dean A. Fennell, Debra H. Josephs, Andrew P. Robinson, Kim Edmonds, Tina Mackay, Mita Afroza Akther, Miriam Mitchison, Sam M. Janes, Giorgia Trevisan, Adrienne M. Flanagan, Alison Cluroe, Henning Walczak, Stuart Horswell, Lena Karapagniotou, Simon Tavaré, Sarah Sarker, Teresa Marafioti, Matt Krebs, Anna Green, Philippe Lamy, Reena Khiroya, Samantha M. Hill, Andrew Tutt, Ashish Chandra, Selvaraju Veeriah, Faye Gishen, Lisa Thompson, Sarah Vaughan, Stacey Stanislaw, Kevin Litchfield, Colin Watts, Caroline Dive, Zayd Tippu, Ron Sinclair, Merche Jimenez-Linan, Lavinia Spain, Lizi Manzano, Zoe Rhodes, Caroline Stirling, Elena Provenzano, Andrew Rowan, Katey S. S. Enfield, Vasiliki Michalarea, Nahid Sheikh, Antonia Toncheva, Charlotte Ferris, James Spicer, Kai-Keen Shiu, Aida Murra, Gerald Langman, Scott Thomas Colville Shepherd, Nicholas McGranahan, Fabio Gomes, Daniel Hochhauser, Hang Xu, Sergio A. Quezada, James Larkin, Siow Ming Lee, Chi-wah Lok, Massimo Loda, Gary Middleton, Hollie Bancroft, Jo Dransfield, David Moore, Jennifer Thomas, Rebecca C. Fitzgerald, Peter Colloby, Annika Fendler, Emma Beddowes, Ultan McDermott, Christopher Abbosh, Uzma Asghar, Martin Forster, John Le Quesne, Katherine F. Leith, Paddy Stone, Bernard Olisemeke, Bruce Tanchel, Laura Farrelly, Grant D. Stewart, Justine Korteweg, Sanjay Jogai, Nnenna Kanu, Desiree Schnidrig, Heidi Rosenbaum, Elaine Borg, Mat Carter, Anthony J. Chalmers, Andrew C. Kidd, Alexandre Harlé, Ula Mahadeva, Crispin T. Hiley, Fiona Byrne, Heather Shaw, Mariam Jamal-Hanjani, Karin A. Oien, Ian Proctor, Joanne Webb, Sioban Fraser, Sarah Howlett, Ruby Stewart, Peter Van Loo, Nadia Yousaf, Tanya Ahmad, Martin Collard, Sanjay Popat, James D. Brenton, Sarah Rudman, Lewis Au, David G. Harrison, Elias Pintus, Patricia Roxburgh, Olivia Curtis, Ben Deakin, Ariana Huebner, Debra Enting, Simranpreet Summan, S. Baijal, Iver Nordentoft, Carol Jones, Haixi Yan, Sebastian Brandner, Tariq Enver, Lara-Rose Iredale, Yvonne Summers, Babu Naidu, Abby Sharp, Stephen Hazell, Aoune Barhoumi, Emma Nye, Robert E. Hynds, Sharmistha Ghosh, Emilia L. Lim, Ben Shum, Nikki Hunter, John Bridgewater, Eleanor Carlyle, Stephan Beck, Nicolai Juul Birkbak, Steve Hazell, Samra Turajlic, Amy Kerr, Ian Tomlinson, Adrian Tookman, Litchfield, Kevin [0000-0002-3725-0914], Birkbak, Nicolai J [0000-0003-1613-9587], Nordentoft, Iver [0000-0003-4856-4086], Dyrskjøt, Lars [0000-0001-7061-9851], Apollo - University of Cambridge Repository, Division of genetics and epidemiology, The institute of cancer research [London], The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Royal Marsden, University of Arizona, University of Western Ontario, Physic and Astronomy Department, University of Western Ontario (UWO), Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Aarhus University Hospital, Cancer Research UK Lung Cancer Centre of Excellence [Londres, Royaume-Uni], University College of London [London] (UCL), Comprehensive Cancer Center, UCL Cancer Institute [University College London], The Wellcome Trust Sanger Institute [Cambridge], Research Department of Pathology, Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Department of histopathology, University College Hospital, Mammalian Genetics Laboratory, Centre for Research on Adaptive Nanostructures and Nanodevices, Trinity College Dublin, Cancer Research UK London Research Institute, Guy's and St Thomas' Hospital [London], Breakthrough Breast Cancer Centre, London Institute of Cancer, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, University of Cambridge [UK] (CAM), Cancer Division [Sydney, Australia] (The Kinghorn Cancer Centre), Garvan Institute of Medical Research [Sydney, Australia], Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, University of Leicester, Experimental Cancer Medicine Centre, University of Southampton-Faculty of Medicine, Moses, Wittemyer, Harrison and Woodruff, P.C., University of Oxford, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), and Garvan Institute of medical research
- Subjects
0301 basic medicine ,tumor sequencing ,medicine.medical_specialty ,Sampling protocol ,tumor mutational burden ,tumor sampling ,Lung Neoplasms ,molecular profiling ,Biopsy ,homogenization ,Tissue sample ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Humans ,Solid tumor ,lcsh:QH301-705.5 ,Representative sampling ,medicine.diagnostic_test ,Manchester Cancer Research Centre ,ResearchInstitutes_Networks_Beacons/mcrc ,Clonal structure ,biomarkers ,High-Throughput Nucleotide Sequencing ,Tumor tissue ,tumor hetereogeneity ,Tumor Burden ,030104 developmental biology ,lcsh:Biology (General) ,representative sampling ,Urinary Bladder Neoplasms ,Mutation ,Radiology ,030217 neurology & neurosurgery - Abstract
International audience; Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias isinherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mmbiopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB butlow clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure.
- Published
- 2020
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