RT Journal Article SR Electronic T1 Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours JF bioRxiv FD Cold Spring Harbor Laboratory SP 165746 DO 10.1101/165746 A1 Elisa Izquierdo A1 Lina Yuan A1 Sally George A1 Michael Hubank A1 Chris Jones A1 Paula Proszek A1 Janet Shipley A1 Susanne A Gatz A1 Caedyn Stinson A1 Andrew S. Moore A1 Steven C. Clifford A1 Debbie Hicks A1 Janet Lindsey A1 Rebecca Hill A1 Thomas S. Jacques A1 Jane Chalker A1 Khin Thway A1 Simon O’Connor A1 Lynley Marshall A1 Lucas Moreno A1 Andrew Pearson A1 Louis Chesler A1 Brian A. Walker A1 David Gonzalez De Castro YR 2017 UL http://biorxiv.org/content/early/2017/07/27/165746.abstract AB 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.