Validation of CZECANCA (CZEch CAncer paNel for Clinical Application) for targeted NGS-based analysis of hereditary cancer syndromes

Autor: Soukupova, Jana, Zemankova, Petra, Lhotova, Klara, Janatova, Marketa, Borecka, Marianna, Stolarova, Lenka, Lhota, Filip, Foretova, Lenka, Machackova, Eva, Stranecky, Viktor, Tavandzis, Spiros, Kleiblova, Petra, Vocka, Michal, Hartmannova, Hana, Hodanova, Katerina, Kmoch, Stanislav, Kleibl, Zdenek
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Next-Generation Sequencing
Male
DNA Copy Number Variations
Molecular biology
Bioinformatics
Genetic Causes of Cancer
lcsh:Medicine
DNA fragmentation
DNA replication
Biochemistry
Sensitivity and Specificity
Database and Informatics Methods
Sequencing techniques
INDEL Mutation
Diagnostic Medicine
Neoplastic Syndromes
Hereditary
Medicine and Health Sciences
Genetics
Cancer Detection and Diagnosis
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
DNA sequencing
Genome Sequencing
Genetic Testing
lcsh:Science
Genetic Association Studies
Biology and life sciences
Cancer Risk Factors
lcsh:R
Computational Biology
High-Throughput Nucleotide Sequencing
Reproducibility of Results
DNA
Genomics
Genome Analysis
Nucleic acids
Research and analysis methods
Molecular biology techniques
Oncology
Mutation
Female
lcsh:Q
Transcriptome Analysis
Research Article
Zdroj: PLoS ONE, Vol 13, Iss 4, p e0195761 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: Background Carriers of mutations in hereditary cancer predisposition genes represent a small but clinically important subgroup of oncology patients. The identification of causal germline mutations determines follow-up management, treatment options and genetic counselling in patients’ families. Targeted next-generation sequencing-based analyses using cancer-specific panels in high-risk individuals have been rapidly adopted by diagnostic laboratories. While the use of diagnosis-specific panels is straightforward in typical cases, individuals with unusual phenotypes from families with overlapping criteria require multiple panel testing. Moreover, narrow gene panels are limited by our currently incomplete knowledge about possible genetic dispositions. Methods We have designed a multi-gene panel called CZECANCA (CZEch CAncer paNel for Clinical Application) for a sequencing analysis of 219 cancer-susceptibility and candidate predisposition genes associated with frequent hereditary cancers. Results The bioanalytical and bioinformatics pipeline was validated on a set of internal and commercially available DNA controls showing high coverage uniformity, sensitivity, specificity and accuracy. The panel demonstrates a reliable detection of both single nucleotide and copy number variants. Inter-laboratory, intra- and inter-run replicates confirmed the robustness of our approach. Conclusion The objective of CZECANCA is a nationwide consolidation of cancer-predisposition genetic testing across various clinical indications with savings in costs, human labor and turnaround time. Moreover, the unified diagnostics will enable the integration and analysis of genotypes with associated phenotypes in a national database improving the clinical interpretation of variants.
Databáze: OpenAIRE
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