A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations

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 alterat...

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Detalles Bibliográficos
Autores: George, Sally L., Izquierdo, Elisa, Campbell, James, Koutroumanidou, Eleni, Proszek, Paula, Jamal, Sabri, Hughes, Deborah, Yuan, Lina, Marshall, Lynley V., Carceller Benito, Fernando, Chisholm, Julia C., Vaidya, Sucheta, Mandeville, Henry, Angelini, Paola, Wasti, Ajla, Bexelius, Tomas, Thway, Khin, Gatz, Susanne A., Clarke, Matthew, Al-Lazikani, Bissan, Barone, Giuseppe, Anderson, John, Tweddle, Deborah A., González, David, Walker, Brian A., Barton, Jack, Depani, Sarita, Eze, Jessica, Ahmed, Saira W., Moreno, Lucas, Pearson, Andrew, Shipley, Janet, Jones, Chris, Hargrave, Darren, Jacques, Thomas S., Hubank, Michael, Chesler, Louis
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/691278
Acceso en línea:http://hdl.handle.net/10486/691278
https://dx.doi.org/10.1016/j.ejca.2019.07.027
Access Level:acceso abierto
Palabra clave:Paediatric oncology
Clinical targeted sequencing
Personalised medicine
Circulating tumour DNA
Medicina
Descripción
Sumario: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.

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