TumorNext: A comprehensive tumor profiling assay that incorporates high resolution copy number analysis and germline status to improve testing accuracy
| Autor: | Phillip Gray, Swati Shah, Lisa Uyeda, Elizabeth R. Plimack, Matthew Zibelman, Marijo Bilusic, Lavinia Dobrea, Hsaio Mei Lu, Huy Gia Vuong, Vickie Hsuan, Aaron Elliott, Mike Janicek, Wenbo Mu, Lawrence D. Wagman, Jayne Hoo, Erica A. Golemis, Harshil Patel, Susanne Fox, Pei Tsai, Sandra Brown, Ranee Mehra |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Tissue Fixation DNA Copy Number Variations Somatic cell actionable mutations DNA Mutational Analysis Copy number analysis Biology Polymorphism Single Nucleotide DNA sequencing Germline 03 medical and health sciences 0302 clinical medicine Germline mutation Gene Frequency Neoplasms Humans Genetic Predisposition to Disease Copy-number variation Gene Genetics next generation sequencing Paraffin Embedding Computational Biology High-Throughput Nucleotide Sequencing Reproducibility of Results tumor profiling 3. Good health Gene Expression Regulation Neoplastic 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mutation germline mutations Research Paper copy number variants |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The development of targeted therapies for both germline and somatic DNA mutations has increased the need for molecular profiling assays to determine the mutational status of specific genes. Moreover, the potential of off-label prescription of targeted therapies favors classifying tumors based on DNA alterations rather than traditional tissue pathology. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext, which can detect single nucleotide variants, small insertions and deletions in 142 genes that are frequently mutated in somatic and/or germline cancers. TumorNext also detects gene fusions and structural variants, such as tandem duplications and inversions, in 15 frequently disrupted oncogenes and tumor suppressors. The assay uses a matched control and custom bioinformatics pipeline to differentiate between somatic and germline mutations, allowing precise variant classification. We tested 170 previously characterized samples, of which > 95% were formalin-fixed paraffin embedded tissue from 8 different cancer types, and highlight examples where lack of germline status may have led to the inappropriate prescription of therapy. We also describe the validation of the Affymetrix OncoScan platform, an array technology for high resolution copy number variant detection for use in parallel with the NGS panel that can detect single copy amplifications and hemizygous deletions. We analyzed 80 previously characterized formalin-fixed paraffin-embedded specimens and provide examples of hemizygous deletion detection in samples with known pathogenic germline mutations. Thus, the TumorNext combined approach of NGS and OncoScan potentially allows for the identification of the "second hit" in hereditary cancer patients. |
| Databáze: | OpenAIRE |
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