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Clinical whole-genome sequencing from routine formalin-fixed, paraffin-embedded specimens: pilot study for the 100,000 Genomes Project.
Robbe, Pauline; Popitsch, Niko; Knight, Samantha J L; Antoniou, Pavlos; Becq, Jennifer; He, Miao; Kanapin, Alexander; Samsonova, Anastasia; Vavoulis, Dimitrios V; Ross, Mark T; Kingsbury, Zoya; Cabes, Maite; Ramos, Sara D C; Page, Suzanne; Dreau, Helene; Ridout, Kate; Jones, Louise J; Tuff-Lacey, Alice; Henderson, Shirley; Mason, Joanne; Buffa, Francesca M; Verrill, Clare; Maldonado-Perez, David; Roxanis, Ioannis; Collantes, Elena; Browning, Lisa; Dhar, Sunanda; Damato, Stephen; Davies, Susan; Caulfield, Mark; Bentley, David R; Taylor, Jenny C; Turnbull, Clare; Schuh, Anna.
Afiliación
  • Robbe P; Oxford Molecular Diagnostics Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. pauline.robbe@ndcls.ox.ac.uk.
  • Popitsch N; Wellcome Trust Centre of Human Genetics, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Knight SJL; Wellcome Trust Centre of Human Genetics, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Antoniou P; Oxford Molecular Diagnostics Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Becq J; Illumina Cambridge Ltd., Chesterford Research Park, Saffron Walden, UK.
  • He M; Illumina Cambridge Ltd., Chesterford Research Park, Saffron Walden, UK.
  • Kanapin A; Department of Oncology, University of Oxford, Oxford, UK.
  • Samsonova A; Department of Oncology, University of Oxford, Oxford, UK.
  • Vavoulis DV; Oxford Molecular Diagnostics Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Ross MT; Illumina Cambridge Ltd., Chesterford Research Park, Saffron Walden, UK.
  • Kingsbury Z; Illumina Cambridge Ltd., Chesterford Research Park, Saffron Walden, UK.
  • Cabes M; Oxford Molecular Diagnostics Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
  • Ramos SDC; Oxford Molecular Diagnostics Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
  • Page S; Oxford Molecular Diagnostics Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
  • Dreau H; Oxford Molecular Diagnostics Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
  • Ridout K; Oxford Molecular Diagnostics Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Jones LJ; Genomics England, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Tuff-Lacey A; Genomics England, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Henderson S; Oxford Molecular Diagnostics Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
  • Mason J; Genomics England, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Buffa FM; Computational Biology and Integrative Genomics, Department of Oncology, University of Oxford, Oxford, UK.
  • Verrill C; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Maldonado-Perez D; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Roxanis I; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Collantes E; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Browning L; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Dhar S; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Damato S; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Davies S; Department of Cellular Pathology, Oxford University Hospital Foundation Trust, Oxford, UK.
  • Caulfield M; Genomics England, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Bentley DR; NIHR Biomedical Research Centre at Barts Health NHS Trust, London, UK.
  • Taylor JC; Illumina Cambridge Ltd., Chesterford Research Park, Saffron Walden, UK.
  • Turnbull C; Wellcome Trust Centre of Human Genetics, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Schuh A; NIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Genet Med ; 20(10): 1196-1205, 2018 10.
Article en En | MEDLINE | ID: mdl-29388947
ABSTRACT

PURPOSE:

Fresh-frozen (FF) tissue is the optimal source of DNA for whole-genome sequencing (WGS) of cancer patients. However, it is not always available, limiting the widespread application of WGS in clinical practice. We explored the viability of using formalin-fixed, paraffin-embedded (FFPE) tissues, available routinely for cancer patients, as a source of DNA for clinical WGS.

METHODS:

We conducted a prospective study using DNAs from matched FF, FFPE, and peripheral blood germ-line specimens collected from 52 cancer patients (156 samples) following routine diagnostic protocols. We compared somatic variants detected in FFPE and matching FF samples.

RESULTS:

We found the single-nucleotide variant agreement reached 71% across the genome and somatic copy-number alterations (CNAs) detection from FFPE samples was suboptimal (0.44 median correlation with FF) due to nonuniform coverage. CNA detection was improved significantly with lower reverse crosslinking temperature in FFPE DNA extraction (80 °C or 65 °C depending on the methods). Our final data showed somatic variant detection from FFPE for clinical decision making is possible. We detected 98% of clinically actionable variants (including 30/31 CNAs).

CONCLUSION:

We present the first prospective WGS study of cancer patients using FFPE specimens collected in a routine clinical environment proving WGS can be applied in the clinic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genoma Humano / Variaciones en el Número de Copia de ADN / Secuenciación Completa del Genoma / Neoplasias Tipo de estudio: Guideline / Observational_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genoma Humano / Variaciones en el Número de Copia de ADN / Secuenciación Completa del Genoma / Neoplasias Tipo de estudio: Guideline / Observational_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido