Representative sequencing: unbiased sampling of solid tumor tissue

Litchfield, K. et al. (2020) Representative sequencing: unbiased sampling of solid tumor tissue. Cell Reports, 31(5), 107550. (doi: 10.1016/j.celrep.2020.107550) (PMID:32375028)

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Abstract

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.

Item Type:Articles
Additional Information:University of Glasgow authors are members of the PEACE Consortium.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Biankin, Professor Andrew and Le Quesne, Professor John and Blyth, Professor Kevin and Fraser, Dr Sioban and Oien, Professor Karin and Chalmers, Professor Anthony and Roxburgh, Dr Patricia and Kidd, Mr Andrew
Authors: Litchfield, K., Stanislaw, S., Spain, L., Gallegos, L. L., Rowan, A., Schnidrig, D., Rosenbaum, H., Harle, A., Au, L., Hill, S. M., Tippu, Z., Thomas, J., Thompson, L., Xu, H., Horswell, S., Barhoumi, A., Jones, C., Leith, K. F., Burgess, D. L., Watkins, T. B.K., Lim, E., Birkbak, N. J., Lamy, P., Nordentoft, I., Dyrskjøt, L., Pickering, L., Hazell, S., Jamal-Hanjani, M., Larkin, J., Swanton, C., Alexander, N. R., Turajlic, S., Abbosh, C., Shiu, K.-K., Bridgewater, J., Hochhauser, D., Forster, M., Lee, S.-M., Ahmad, T., Papadatos-Pastos, D., Janes, S., Van Loo, P., Enfield, K., McGranahan, N., Huebner, A., Quezada, S., Beck, S., Parker, P., Walczak, H., Enver, T., Hynds, R., Falzon, M., Proctor, I., Sinclair, R., Lok, C.-w., Rhodes, Z., Moore, D., Marafioti, T., Borg, E., Mitchison, M., Khiroya, R., Trevisan, G., Ellery, P., Linch, M., Brandner, S., Hiley, C., Veeriah, S., Razaq, M., Shaw, H., Attard, G., Akther, M. A., Naceur-Lombardelli, C., Manzano, L., Al-Bakir, M., Summan, S., Kanu, N., Ward, S., Asghar, U., Lim, E., Gishen, F., Tookman, A., Stone, P., Stirling, C., Furness, A., Edmonds, K., Hunter, N., Sarker, S., Vaughan, S., Mangwende, M., Pearce, K., Spain, L., Shepherd, S., Yan, H., Shum, B., Carlyle, E., Hazell, S., Fendler, A., Byrne, F., Yousaf, N., Popat, S., Curtis, O., Stamp, G., Toncheva, A., Nye, E., Murra, A., Korteweg, J., Sheikh, N., Josephs, D., Chandra, A., Spicer, J., Mahadeva, U., Green, A., Stewart, R., Iredale, L.-R., Mackay, T., Deakin, B., Enting, D., Rudman, S., Ghosh, S., Karapagniotou, L., Pintus, E., Tutt, A., Howlett, S., Michalarea, V., Brenton, J., Caldas, C., Fitzgerald, R., Jimenez-Linan, M., Provenzano, E., Cluroe, A., Stewart, G., Watts, C., Gilbertson, R., McDermott, U., Tavare, S., Beddowes, E., Roxburgh, P., Biankin, A., Chalmers, A., Fraser, S., Oien, K., Kidd, A., Blyth, K., Krebs, M., Blackhall, F., Summers, Y., Dive, C., Marais, R., Gomes, F., Carter, M., Dransfield, J., Le Quesne, J., Fennell, D., Shaw, J., Naidu, B., Baijal, S., Tanchel, B., Langman, G., Robinson, A., Collard, M., Cockcroft, P., Ferris, C., Bancroft, H., Kerr, A., Middleton, G., Webb, J., Kadiri, S., Colloby, P., Olisemeke, B., Wilson, R., Tomlinson, I., Jogai, S., Ottensmeier, C., Harrison, D., Loda, M., Flanagan, A., McKenzie, M., Hackshaw, A., Ledermann, J., Sharp, A., Farrelly, L., and Bridger, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cell Reports 31(5): 107550
Publisher Policy:Reproduced under a Creative Commons License

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