UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Izquierdo, E; Yuan, L; George, S; Hubank, M; Jones, C; Proszek, P; Shipley, J; ... De Castro, DG; + view all (2017) Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours. Oncotarget , 8 (67) pp. 112036-112050. 10.18632/oncotarget.23000. Green open access

[thumbnail of 23000-324205-4-PB.pdf]
Preview
Text
23000-324205-4-PB.pdf - Published Version

Download (1MB) | Preview

Abstract

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.

Type: Article
Title: Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.23000
Publisher version: http://doi.org/10.18632/oncotarget.23000
Language: English
Additional information: Copyrigh © Izquierdo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: childhood cancer; targeted sequencing; molecular diagnostics; panel validation; targeted therapies
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10041175
Downloads since deposit
97Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item