Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.


  • Jenny Klintman
  • Katerina Barmpouti
  • Samantha J L Knight
  • Pauline Robbe
  • Hélène Dreau
  • Ruth Clifford
  • Kate Ridout
  • Adam Burns
  • Adele Timbs
  • David Bruce
  • Pavlos Antoniou
  • Alona Sosinsky
  • Jennifer Becq
  • David Bentley
  • Peter Hillmen
  • Jenny C Taylor
  • Mark Caulfield
  • Anna H Schuh
Externa organisationer
  • Oxford University Hospital
  • NIHR Biomedical Research Centre, Oxford
  • Genomics England
  • Illumina
  • University of Oxford
  • University Hospital Limerick
  • St James's University Hospital

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
  • Hematologi
  • Cancer och onkologi
Sidor (från-till)412-417
TidskriftBritish Journal of Haematology
StatusPublished - 2018 maj 29
Peer review utfördJa
Externt publiceradJa