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

Research output: Contribution to journalArticle


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
External organisations
  • Oxford University Hospital
  • NIHR Biomedical Research Centre, Oxford
  • Genomics England
  • Illumina
  • University of Oxford
  • University Hospital Limerick
  • St James's University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Hematology
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)412-417
JournalBritish Journal of Haematology
Issue number3
Publication statusPublished - 2018 May 29
Publication categoryResearch
Externally publishedYes