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A comprehensive DNA panel next generation sequencing approach supporting diagnostics and therapy prediction in neurooncology

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Název: A comprehensive DNA panel next generation sequencing approach supporting diagnostics and therapy prediction in neurooncology
Autoři: Lorenz, Julia, Rothhammer-Hampl, Tanja, Zoubaa, Saida, Bumes, Elisabeth, Pukrop, Tobias, Kölbl, Oliver, Corbacioglu, Selim, Schmidt, Nils O., Proescholdt, Martin A., Hau, Peter, Riemenschneider, Markus J.
Zdroj: Acta Neuropathol Commun
Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-15 (2020)
Informace o vydavateli: Springer Science and Business Media LLC, 2020.
Rok vydání: 2020
Témata: Adult, Male, 610 Medizin, Medical Oncology, Targeted therapy, Next generation sequencing, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, Molecular Targeted Therapy, Precision Medicine, RC346-429, ddc:610, Brain Neoplasms, Research, High-Throughput Nucleotide Sequencing, Glioma, Sequence Analysis, DNA, 3. Good health, Female [MeSH], High-Throughput Nucleotide Sequencing/methods [MeSH], Brain Neoplasms/genetics [MeSH], Adult [MeSH], Medulloblastoma, Humans [MeSH], Medical Oncology/methods [MeSH], Precision Medicine/methods [MeSH], Glioblastoma, Antineoplastic Combined Chemotherapy Protocols/therapeutic use [MeSH], Male [MeSH], Integrated diagnoses, Biomarkers, Tumor/genetics [MeSH], Neurology/methods [MeSH], Sequence Analysis, DNA [MeSH], Brain Neoplasms/drug therapy [MeSH], Molecular Targeted Therapy/methods [MeSH], Meningioma, Neurology, Female, Neurology. Diseases of the nervous system, Glioblastoma, Glioma, Meningioma, Medulloblastoma, Next generation sequencing, Targeted therapy, Integrated diagnoses
Popis: Recent updates in the classification of central nervous system (CNS) tumors have increased the need for molecular testing. Assessment of multiple alterations in parallel, complex combinations of gene sequence and chromosomal changes, as well as therapy prediction by identification of actionable mutations are the major challenges. We here report on a customized next generation sequencing (NGS)-based DNA panel assay that combines diagnostic and predictive testing and -as a comprehensive approach- allows for simultaneous single nucleotide variant (SNP) / small insertion/deletion (InDel), copy number variation (CNV) and loss of heterozygosity (LOH) detection. We analyzed formalin-fixed and paraffin-embedded (FFPE) DNA from a total of 104 patients with CNS tumors. After amplicon capture-based library preparation, sequencing was performed on the relatively cost-efficient Illiumina MiniSeq platform and evaluated with freely available bioinformatical tools. 57 genes for exonic SNP/InDel calling (19 of those in intronic regions for CNV analysis), 3 chromosomal arms and 4 entire chromosomes for CNV and LOH analysis were covered. Results were extensively validated. Our approach yielded high accuracy, sensitivity and specificity. It led to refined diagnoses in a relevant number of analyzed cases, reliably enabled complex subclassifications (e.g. for medulloblastomas) and identified actionable targets for clinical use. Thus, our single-platform approach is an efficient and powerful tool to comprehensively support molecular testing in neurooncology. Future functionality is guaranteed as novel upcoming biomarkers can be easily incorporated in a modular panel design.
Druh dokumentu: Article
Conference object
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 2051-5960
DOI: 10.1186/s40478-020-01000-w
DOI: 10.5283/epub.44985
DOI: 10.5283/epub.4498510.1186/s40478-020-01000-w
Přístupová URL adresa: https://actaneurocomms.biomedcentral.com/track/pdf/10.1186/s40478-020-01000-w
https://pubmed.ncbi.nlm.nih.gov/32758285
https://doaj.org/article/430d4af534e348c3b9b1dea1af301bbe
https://epub.uni-regensburg.de/44985/
https://link.springer.com/content/pdf/10.1186/s40478-020-01000-w.pdf
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-020-01000-w
https://pubmed.ncbi.nlm.nih.gov/32758285/
https://link.springer.com/article/10.1186/s40478-020-01000-w
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405456
https://repository.publisso.de/resource/frl:6452344
https://epub.uni-regensburg.de/44985/
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....ff370c4ed82ab1cd013cf367731446c1
Databáze: OpenAIRE
Popis
Abstrakt:Recent updates in the classification of central nervous system (CNS) tumors have increased the need for molecular testing. Assessment of multiple alterations in parallel, complex combinations of gene sequence and chromosomal changes, as well as therapy prediction by identification of actionable mutations are the major challenges. We here report on a customized next generation sequencing (NGS)-based DNA panel assay that combines diagnostic and predictive testing and -as a comprehensive approach- allows for simultaneous single nucleotide variant (SNP) / small insertion/deletion (InDel), copy number variation (CNV) and loss of heterozygosity (LOH) detection. We analyzed formalin-fixed and paraffin-embedded (FFPE) DNA from a total of 104 patients with CNS tumors. After amplicon capture-based library preparation, sequencing was performed on the relatively cost-efficient Illiumina MiniSeq platform and evaluated with freely available bioinformatical tools. 57 genes for exonic SNP/InDel calling (19 of those in intronic regions for CNV analysis), 3 chromosomal arms and 4 entire chromosomes for CNV and LOH analysis were covered. Results were extensively validated. Our approach yielded high accuracy, sensitivity and specificity. It led to refined diagnoses in a relevant number of analyzed cases, reliably enabled complex subclassifications (e.g. for medulloblastomas) and identified actionable targets for clinical use. Thus, our single-platform approach is an efficient and powerful tool to comprehensively support molecular testing in neurooncology. Future functionality is guaranteed as novel upcoming biomarkers can be easily incorporated in a modular panel design.
ISSN:20515960
DOI:10.1186/s40478-020-01000-w