Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue

التفاصيل البيبلوغرافية
العنوان: Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue
المؤلفون: Litchfield, Kevin, Stanislaw, Stacey, Spain, Lavinia, Gallegos, Lisa L., Rowan, Andrew, Schnidrig, Desiree, Rosenbaum, Heidi, Harle, Alexandre, Au, Lewis, Hill, Samantha M., Tippu, Zayd, Thomas, Jennifer, Thompson, Lisa, Xu, Hang, Horswell, Stuart, Barhoumi, Aoune, Jones, Carol, Leith, Katherine F., Burgess, Daniel L., Watkins, Thomas B.K., Lim, Emilia, Birkbak, Nicolai J., Lamy, Philippe, Nordentoft, Iver, Dyrskjøt, Lars, Pickering, Lisa, Hazell, Stephen, Jamal-Hanjani, Mariam, Abbosh, Chris, Shiu, Kai-Keen, Bridgewater, John, Hochhauser, Daniel, Forster, Martin, Lee, Siow-Ming, Ahmad, Tanya, Papadatos-Pastos, Dionysis, Janes, Sam, Van Loo, Peter, Enfield, Katey, McGranahan, Nicholas, Huebner, Ariana, Quezada, Sergio, Beck, Stephan, Parker, Peter, Walczak, Henning, Enver, Tariq, Hynds, Rob, Falzon, Mary, Proctor, Ian, Sinclair, Ron, Lok, Chi-wah, Rhodes, Zoe, Moore, David, Marafioti, Teresa, Borg, Elaine, Mitchison, Miriam, Khiroya, Reena, Trevisan, Giorgia, Ellery, Peter, Linch, Mark, Brandner, Sebastian, Hiley, Crispin, Veeriah, Selvaraju, Razaq, Maryam, Shaw, Heather, Attard, Gert, Akther, Mita Afroza, Naceur-Lombardelli, Cristina, Manzano, Lizi, Al-Bakir, Maise, Summan, Simranpreet, Kanu, Nnenna, Ward, Sophie, Asghar, Uzma, Lim, Emilia, Gishen, Faye, Tookman, Adrian, Stone, Paddy, Stirling, Caroline, Furness, Andrew, Edmonds, Kim, Hunter, Nikki, Sarker, Sarah, Vaughan, Sarah, Mangwende, Mary, Pearce, Karla, Spain, Lavinia, Shepherd, Scott, Yan, Haixi, Shum, Ben, Carlyle, Eleanor, Hazell, Steve, Fendler, Annika, Byrne, Fiona, Yousaf, Nadia, Popat, Sanjay, Curtis, Olivia, Stamp, Gordon, Toncheva, Antonia, Nye, Emma, Murra, Aida, Korteweg, Justine, Sheikh, Nahid, Josephs, Debra, Chandra, Ashish, Spicer, James, Mahadeva, Ula, Green, Anna, Stewart, Ruby, Iredale, Lara-Rose, Mackay, Tina, Deakin, Ben, Enting, Debra, Rudman, Sarah, Ghosh, Sharmistha, Karapagniotou, Lena, Pintus, Elias, Tutt, Andrew, Howlett, Sarah, Michalarea, Vasiliki, Brenton, James, Caldas, Carlos, Fitzgerald, Rebecca, Jimenez-Linan, Merche, Provenzano, Elena, Cluroe, Alison, Stewart, Grant, Watts, Colin, Gilbertson, Richard, McDermott, Ultan, Tavare, Simon, Beddowes, Emma, Roxburgh, Patricia, Biankin, Andrew, Chalmers, Anthony, Fraser, Sioban, Oien, Karin, Kidd, Andrew, Blyth, Kevin, Krebs, Matt, Blackhall, Fiona, Summers, Yvonne, Dive, Caroline, Marais, Richard, Gomes, Fabio, Carter, Mat, Dransfield, Jo, Le Quesne, John, Fennell, Dean, Shaw, Jacqui, Naidu, Babu, Baijal, Shobhit, Tanchel, Bruce, Langman, Gerald, Robinson, Andrew, Collard, Martin, Cockcroft, Peter, Ferris, Charlotte, Bancroft, Hollie, Kerr, Amy, Middleton, Gary, Webb, Joanne, Kadiri, Salma, Colloby, Peter, Olisemeke, Bernard, Wilson, Rodelaine, Tomlinson, Ian, Jogai, Sanjay, Ottensmeier, Christian, Harrison, David, Loda, Massimo, Flanagan, Adrienne, McKenzie, Mairead, Hackshaw, Allan, Ledermann, Jonathan, Sharp, Abby, Farrelly, Laura, Bridger, Hayley, Larkin, James, Swanton, Charles, Alexander, Nelson R., Turajlic, Samra
المصدر: Cell Reports; May 2020, Vol. 31 Issue: 5
مستخلص: Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mm biopsy), 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 but low 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.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:22111247
DOI:10.1016/j.celrep.2020.107550