A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations
Author
George, Sally L.; Izquierdo, Elisa; Campbell, James; Koutroumanidou, Eleni; Proszek, Paula; Jamal, Sabri; Hughes, Deborah; Yuan, Lina; Marshall, Lynley V.; Carceller Benito, Fernando
Entity
UAM. Departamento de CirugíaPublisher
Elsevier Ltd.Date
2019-07-19Citation
10.1016/j.ejca.2019.07.027
European Journal of Cancer 121 (2019): 224-235
ISSN
0959-8049DOI
10.1016/j.ejca.2019.07.027Funded by
This work was supported by Christopher’s Smile, the National Institute of Health Research (NIHR) Royal Marsden Biomedical Research Centre (BRC), Children With Cancer UK (CWC UK) Cancer Research UK (CRUK), Abbie’s Fund, the Rosetree Trust and the KiCa Fund, managed by the King Baudouin Foundation. Roche provided support for Panel development. T.S.J. is funded by The Brain Tumour Charity, CWC UK, GOSH Children’s Charity (GOSH CC), CRUK, the Olivia Hodson Cancer Fund and the NIHR GOSH BRC. J.A. and D.H. are funded by the GOSH CC and NIHR GOSH BRC. L.V.M. is funded by the Oak Foundation. The authors thank all participants and the CCLG Tissue Bank for access to samples and contributing CCLG Centres, including members of the ECMC Paediatric network. The CCLG Tissue Bank is funded by Cancer Research UK and CCLGEditor's Version
https://doi.org/10.1016/j.ejca.2019.07.027Subjects
Paediatric oncology; Clinical targeted sequencing; Personalised medicine; Circulating tumour DNA; MedicinaRights
© 2020 Published by Elsevier Ltd-
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Background: For children with cancer, the clinical integration of precision medicine
to enable predictive biomarkerebased 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)especific 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 panelebased approach can identify actionable genetic alterations in a
high proportion of patients.
Files in this item
Google Scholar:George, Sally L.
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Izquierdo, Elisa
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Campbell, James
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Koutroumanidou, Eleni
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Proszek, Paula
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Jamal, Sabri
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Hughes, Deborah
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Yuan, Lina
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Marshall, Lynley V.
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Carceller Benito, Fernando
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Chisholm, Julia C.
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Vaidya, Sucheta
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Mandeville, Henry
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Angelini, Paola
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Wasti, Ajla
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Bexelius, Tomas
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Thway, Khin
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Gatz, Susanne A.
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Clarke, Matthew
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Al-Lazikani, Bissan
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Barone, Giuseppe
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Anderson, John
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Tweddle, Deborah A.
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González, David
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Walker, Brian A.
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Barton, Jack
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Depani, Sarita
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Eze, Jessica
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Ahmed, Saira W.
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Moreno, Lucas
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Pearson, Andrew
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Shipley, Janet
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Jones, Chris
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Hargrave, Darren
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Jacques, Thomas S.
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Hubank, Michael
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Chesler, Louis
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