EGAGenomicsExome Sequencinghttps://ega-archive.org/studies/EGAS00001007363EGAEGA study EGAS00001007363Towards standardized whole exome sequencing (WES) for cancer patients: lessons from a multicentric pilot studyEGArestrictedPilot, Complete Exome Sequencings, Malignant Neoplasm, Complete Exome, Neoplasms, Exome, Benign Neoplasm, Tumor, Malignant, Client, Exome Sequencing, MT, Benign, Pilot Study., Neoplasm, Studies, Project, Whole Transcriptome, Transcriptome Sequencing, WES, Complete Transcriptome, primary cancer, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Projects, Malignancy, Complete Exome Sequencing, Whole Transcriptome Sequencing, Benign Neoplasms, Cancers, malignant tumor, Sequencing, Malignant Neoplasms, Neoplasias, Study, Pilot Project, Whole Exome, Patient, malignant neoplasm, Clients, Whole, Whole Exome Sequencing, Malignancies, Transcriptome Sequencings, Neoplasia, Pilot Studies, Cancer, TumorsPilot, CG12217, chromosomal crossover, Biological Markers, 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Studies, Immune MarkersfalseTowards standardized whole exome sequencing (WES) for cancer patients: lessons from a multicentric pilot studyA growing number of druggable targets and national initiatives for precision oncology necessitate broader 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 sensitivity between 91-95% and a positive predictive value (PPV) of 82-95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Deviations were observed for cases with 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.2023-07-11 09:56:45EGAS000010073639606EGAD00001011087EGAC00001003313