2026-06-14T05:06:43Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/74102024-11-29T15:30:42Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Izquierdo, Elisa author Yuan, Lina author George, Sally author Hubank, Michael author Jones, Chris author Proszek, Paula author Shipley, Janet author Gatz, Susanne A author Stinson, Caedyn author Moore, Andrew S author Clifford, Steven C author Hicks, Debbie author Lindsey, Janet C author Hill, Rebecca M author Jacques, Thomas S author Chalker, Jane author Thway, Khin author O'Connor, Simon author Marshall, Lynley author Moreno, Lucas author Pearson, Andrew author Chesler, Louis author Walker, Brian A author De Castro, David Gonzalez author 2017-12-19 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. Oncotarget. 2017;8(67):112036-112050. 10.18632/oncotarget.23000 1949-2553 1949-2553 Oncotarget 29340109 http://hdl.handle.net/20.500.12105/7410 Childhood cancer Molecular diagnostics Panel validation Targeted sequencing Targeted therapies Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours