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

Lookup NU author(s): Professor Steven CliffordORCiD, Dr Debbie Hicks, Dr Janet Lindsey, Dr Rebecca Hill



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© Izquierdo et al. 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.

Publication metadata

Author(s): Izquierdo E, Yuan L, George S, Hubank M, Jones C, Proszek P, Shipley J, Gatz SA, Stinson C, Moore AS, Clifford SC, Hicks D, Lindsey JC, Hill RM, Jacques TS, Chalker J, Thway K, O'Connor S, Marshall L, Moreno L, Pearson A, Chesler L, Walker BA, De Castro DG

Publication type: Article

Publication status: Published

Journal: Oncotarget

Year: 2017

Volume: 8

Issue: 67

Pages: 112036-112050

Online publication date: 06/12/2017

Acceptance date: 16/11/2017

Date deposited: 22/01/2018

ISSN (electronic): 1949-2553

Publisher: Impact Journals LLC


DOI: 10.18632/oncotarget.23000


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