TY - JOUR
T1 - A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations
AU - George, Sally L.
AU - Izquierdo, Elisa
AU - Campbell, James
AU - Koutroumanidou, Eleni
AU - Proszek, Paula
AU - Jamal, Sabri
AU - Hughes, Deborah
AU - Yuan, Lina
AU - Marshall, Lynley V.
AU - Carceller, Fernando
AU - Chisholm, Julia C.
AU - Vaidya, Sucheta
AU - Mandeville, Henry
AU - Angelini, Paola
AU - Wasti, Ajla
AU - Bexelius, Tomas
AU - Thway, Khin
AU - Gatz, Susanne A.
AU - Clarke, Matthew
AU - Al-Lazikani, Bissan
AU - Barone, Giuseppe
AU - Anderson, John
AU - Tweddle, Deborah A.
AU - Gonzalez, David
AU - Walker, Brian A.
AU - Barton, Jack
AU - Depani, Sarita
AU - Eze, Jessica
AU - Ahmed, Saira W.
AU - Moreno, Lucas
AU - Pearson, Andrew
AU - Shipley, Janet
AU - Jones, Chris
AU - Hargrave, Darren
AU - Jacques, Thomas S.
AU - Hubank, Michael
AU - Chesler, Louis
N1 - Publisher Copyright:
© 2019
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
KW - Circulating tumour DNA
KW - Clinical targeted sequencing
KW - Paediatric oncology
KW - Personalised medicine
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U2 - 10.1016/j.ejca.2019.07.027
DO - 10.1016/j.ejca.2019.07.027
M3 - Article
C2 - 31543384
AN - SCOPUS:85072699671
SN - 0959-8049
VL - 121
SP - 224
EP - 235
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -