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)

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: Le Quesne, Professor John and Blyth, Professor Kevin and Oien, Professor Karin and Chalmers, Professor Anthony and Biankin, Professor Andrew and Roxburgh, Dr Patricia and Kidd, Mr Andrew and Fraser, Dr Sioban
• 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 > School 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