Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer
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Le résumé fourni par la source
PURPOSE Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored. METHODS We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes. RESULTS During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%). CONCLUSION Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer
- Date Crossref
- 01/06/2023
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Lund University Division of Clinical Genetics pays non établi dans la noticeUniversité ou école supérieure
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Skåne University Hospital Section of Clinical Genetics pays non établi dans la noticeÉtablissement de santé
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Karolinska University Hospital Clinical Pathology and Cancer Diagnostics pays non établi dans la noticeÉtablissement de santé
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Karolinska Institutet Department of Oncology-Pathology pays non établi dans la noticeUniversité ou école supérieure
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Sahlgrenska University Hospital Department of Clinical Genetics and Genomics pays non établi dans la noticeÉtablissement de santé
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University of Gothenburg Department of Laboratory Medicine pays non établi dans la noticeUniversité ou école supérieure
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Linköping University Crown Princess Victoria's Child and Youth Hospital in Linköping pays non établi dans la noticeUniversité ou école supérieure
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Uppsala University Clinical Genetics pays non établi dans la noticeUniversité ou école supérieure
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Uppsala University Hospital pays non établi dans la noticeÉtablissement de santé
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Science for Life Laboratory pays non établi dans la noticeStructure de recherche
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KTH Royal Institute of Technology pays non établi dans la noticeUniversité ou école supérieure
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Umeå University pays non établi dans la noticeUniversité ou école supérieure
Division of Clinical Genetics — Lund University, Section of Clinical Genetics — Skåne University Hospital et Clinical Pathology and Cancer Diagnostics — Karolinska University Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.