Molecular Profiling of Hard-to-Treat Childhood and Adolescent Cancers
| Autor: | Daniel Sinnett, Pierre Teira, Stephanie Vairy, Benjamin Ellezam, Josee Brossard, Fida Khater, Sonia Cellot, Natalie Patey, Dorothée Dal Soglio, Sylvie Langlois, Sophie Dumoucel, Monia Marzouki, Thai Hoa Tran, Bruno Michon, Sébastien Perreault, Nada Jabado, Jean-Marie Leclerc, Thomas Sontag, Caroline Laverdière, Josette Champagne, Pascal St-Onge, Yvan Samson, Henrique Bittencourt, Michel Duval, Nelson Piché |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Male medicine.medical_specialty Adolescent medicine.medical_treatment DNA sequencing Targeted therapy Internal medicine Neoplasms Exome Sequencing Medicine Profiling (information science) Humans Prospective Studies Child Exome sequencing business.industry Sequence Analysis RNA High-Throughput Nucleotide Sequencing General Medicine Pediatric cancer Third line Mutation Feasibility Studies Female RNA extraction business Relevant information |
| Zdroj: | JAMA network open. 2(4) |
| ISSN: | 2574-3805 |
| Popis: | Importance Little progress in pediatric cancer treatment has been noted in the past decade, urging the development of novel therapeutic strategies for adolescents and children with hard-to-treat cancers. Use of comprehensive molecular profiling in the clinical management of children and adolescents with cancer appears a suitable approach to improve patient care and outcomes, particularly for hard-to-treat cases. Objective To assess the feasibility of identifying potentially actionable mutations using next-generation sequencing–based assays in a clinically relevant time frame. Design, Setting, and Participants This diagnostic study reports the results of the TRICEPS study, a prospective genome sequencing study conducted in Quebec, Canada. Participants, aged 18 years or younger at diagnosis, with refractory or relapsed childhood and adolescent cancers were enrolled from April 2014 through January 2018. Whole-exome sequencing (WES) of matched tumor normal samples and RNA sequencing of tumor were performed to identify single-nucleotide variants, fusion transcripts, differential gene expression, and copy number alterations. Results reviewed by a team of experts were further annotated, synthesized into a report, and subsequently discussed in a multidisciplinary molecular tumor board. Main Outcomes and Measures Molecular profiling of pediatric patients with hard-to-treat cancer, identification of actionable and targetable alteration needed for the management of these patients, and proposition of targeted and personalized novel therapeutic strategies. Results A total of 84 patients with hard-to-treat cancers were included in the analysis. These patients had a mean (range) age of 10.1 (1-21) years and a similar proportion of male (45 [54%]) and female (39 [46%]). Sixty-two patients (74%) had suitable tissues for multimodal molecular profiling (WES and RNA sequencing). The process from DNA or RNA isolation to genomic sequencing and data analysis steps took a median (range) of 24 (4-41) days. Potentially actionable alterations were identified in 54 of 62 patients (87%). Actions were taken in 22 of 54 patients (41%), and 18 (33%) either were on a second or third line of treatment, were in remission, or had stable disease and thus no actions were taken. Conclusions and Relevance Incorporating genomic sequencing into the management of hard-to-treat childhood and adolescent cancers appeared feasible; molecular profiling may enable the identification of potentially actionable alterations with clinical implications for most patients, including targeted therapy and clinically relevant information of diagnostic, prognostic, and monitoring significance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|