George, SL;
Izquierdo, E;
Campbell, J;
Koutroumanidou, E;
Proszek, P;
Jamal, S;
Hughes, D;
... Chesler, L; + view all
(2019)
A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations.
European Journal of Cancer
10.1016/j.ejca.2019.07.027.
Preview |
Text
PIIS0959804919304460-2.pdf - Published Version Download (2MB) | Preview |
Abstract
Background: For children with cancer, the clinical integration of precision medicine to enable predictive biomarker–based therapeutic stratification is urgently needed. / Methods: We have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)–specific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings. / Results: A total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma. / Conclusion: We demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panel–based approach can identify actionable genetic alterations in a high proportion of patients.
| Type: | Article |
|---|---|
| Title: | A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejca.2019.07.027 |
| Publisher version: | https://doi.org/10.1016/j.ejca.2019.07.027 |
| Language: | English |
| Additional information: | Crown Copyright © 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Paediatric oncology, Clinical targeted sequencing, Personalised medicine, Circulating tumour DNA |
| 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-pp.ucl.ac.uk/id/eprint/10082251 |
Archive Staff Only
 |
View Item |
