Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients.

Journal

NPJ precision oncology

ISSN: 2397-768X

Titre abrégé: NPJ Precis Oncol

Pays: England

ID NLM: 101708166

Informations de publication

Date de publication:
20 Oct 2023

Historique:

received: 03 04 2023

accepted: 26 09 2023

medline: 21 10 2023

pubmed: 21 10 2023

entrez: 20 10 2023

Statut: epublish

Résumé

A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.

Identifiants

DOI: 10.1038/s41698-023-00457-x PMID: 37864096 PMC: PMC10589320

pubmed: 37864096

doi: 10.1038/s41698-023-00457-x

pii: 10.1038/s41698-023-00457-x

pmc: PMC10589320

doi:

Types de publication

Journal Article

Langues

eng

Pagination

106

Informations de copyright

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