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Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue.
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; Larkin, James; Swanton, Charles; Alexander, Nelson R; Turajlic, Samra.
Afiliação
  • Litchfield K; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Stanislaw S; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA.
  • Spain L; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Gallegos LL; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA.
  • Rowan A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Schnidrig D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Rosenbaum H; Roche Sequencing Solutions, Madison, 500 S. Rosa Road, Madison, WI 53719, USA.
  • Harle A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Université de Lorraine, CNRS UMR 7039 CRAN, Institut de Cancérologie de Lorraine, Service de Biopathologie, 54000 Nancy, France.
  • Au L; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Hill SM; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA; Department of Cancer Biology, University of Arizona Cancer Center, Tucson, AZ 85724, USA.
  • Tippu Z; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Thomas J; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Thompson L; The Centre for Molecular Pathology, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Xu H; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Horswell S; Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London NW1 1AT, UK.
  • Barhoumi A; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA.
  • Jones C; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA.
  • Leith KF; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA.
  • Burgess DL; Roche Sequencing Solutions, Madison, 500 S. Rosa Road, Madison, WI 53719, USA.
  • Watkins TBK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Lim E; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Birkbak NJ; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Lamy P; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Nordentoft I; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Dyrskjøt L; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Pickering L; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Hazell S; Histopathology Department, Royal Marsden NHS Foundation Trust, London and Sutton, UK.
  • Jamal-Hanjani M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Department of Medical Oncology, University College London Hospitals, London, UK.
  • Larkin J; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
  • Swanton C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Department of Medical Oncology, University College London Hospitals, Londo
  • Alexander NR; Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ 85755, USA. Electronic address: nelson.alexander@roche.com.
  • Turajlic S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK. Electronic address: samra.turajlic@crick.ac.uk.
Cell Rep ; 31(5): 107550, 2020 05 05.
Article em En | MEDLINE | ID: mdl-32375028
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Biomarcadores Tumorais / Carga Tumoral / Sequenciamento de Nucleotídeos em Larga Escala / Neoplasias Pulmonares Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Biomarcadores Tumorais / Carga Tumoral / Sequenciamento de Nucleotídeos em Larga Escala / Neoplasias Pulmonares Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article