Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours

Research output: Contribution to journalArticlepeer-review


  • Elisa Izquierdo
  • Lina Yuan
  • Sally George
  • Michael Hubank
  • Chris Jones
  • Paula Proszek
  • Janet Shipley
  • Caedyn Stinson
  • Andrew S Moore
  • Steven C Clifford
  • Debbie Hicks
  • Janet C Lindsey
  • Rebecca M Hill
  • Thomas S Jacques
  • Jane Chalker
  • Khin Thway
  • Simon O'Connor
  • Lynley Marshall
  • Lucas Moreno
  • Andrew Pearson
  • Louis Chesler
  • Brian A Walker
  • David Gonzalez De Castro

Colleges, School and Institutes

External organisations

  • The Institute of Cancer Research
  • Royal Marsden NHS Foundation Trust
  • University of Queensland
  • Newcastle University
  • University College London
  • HNJ-CNIO Clinical Research Unit and Hospital Universitario Niño Jesus, Madrid, Spain.
  • University of Arkansas
  • Queen's University, Belfast


The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in high-risk patients with unmet need, we have developed a clinically relevant targeted sequencing panel spanning 311 kb and comprising 78 genes involved in childhood cancers. A total of 132 samples were used for the validation of the panel, including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient samples. Cell blends containing known single nucleotide variants (SNVs, n=528) and small insertion-deletions (indels n=108) were used to define panel sensitivities of ≥98% for SNVs and ≥83% for indels [95% CI] and panel specificity of ≥98% [95% CI] for SNVs. FFPE samples performed comparably to FF samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33 clinical specimens and 13 cell lines (including SNVs, indels, amplifications, rearrangements and chromosome losses), 94 (98.9%) were detected by our approach. We have validated a robust and practical methodology to guide clinical management of children with solid tumours based on their molecular profiles. Our work demonstrates the value of targeted gene sequencing in the development of precision medicine strategies in paediatric oncology.


Original languageEnglish
Pages (from-to)112036-112050
Number of pages15
Issue number67
Publication statusPublished - 6 Dec 2017

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