TY - JOUR T1 - Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours JF - bioRxiv DO - 10.1101/165746 SP - 165746 AU - Elisa Izquierdo AU - Lina Yuan AU - Sally George AU - Michael Hubank AU - Chris Jones AU - Paula Proszek AU - Janet Shipley AU - Susanne A Gatz AU - Caedyn Stinson AU - Andrew S. Moore AU - Steven C. Clifford AU - Debbie Hicks AU - Janet Lindsey AU - Rebecca Hill AU - Thomas S. Jacques AU - Jane Chalker AU - Khin Thway AU - Simon O’Connor AU - Lynley Marshall AU - Lucas Moreno AU - Andrew Pearson AU - Louis Chesler AU - Brian A. Walker AU - David Gonzalez De Castro Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/27/165746.abstract N2 - 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. ER -