Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue.

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Embargo End Date

ICR Authors

Litchfield, Kevin
 Au, Lewis
 Larkin, James
 Turajlic, Samra

Authors

Litchfield, K
Stanislaw, S
Spain, L
Gallegos, LL
Rowan, A
Schnidrig, D
Rosenbaum, H
Harle, A
Au, L
Hill, SM
Tippu, Z
Thomas, J
Thompson, L
Xu, H
Horswell, S
Barhoumi, A
Jones, C
Leith, KF
Burgess, DL
Watkins, TBK
Lim, E
Birkbak, NJ
Lamy, P
Nordentoft, I
Dyrskjøt, L
Pickering, L
Hazell, S
Jamal-Hanjani, M
PEACE Consortium,
Larkin, J
Swanton, C
Alexander, NR
Turajlic, S

Document Type

Journal Article

Date

2020-05-05

Date Accepted

2020-04-01

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.

Citation

Cell Reports, 2020, 31 (5), pp. 107550 -

DOI

10.1016/j.celrep.2020.107550

URI

https://repository.icr.ac.uk/handle/internal/5344

Rights

https://creativecommons.org/licenses/by-nc-nd/4.0/

Source Title

Cell Reports

Publisher

CELL PRESS

ISSN

2211-1247

eISSN

2211-1247
2211-1247

Collections

Clinical Studies

Research Team

Molec & Popul Genetics
Melanoma & Kidney Cancer

Notes