Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors12
| العنوان: | Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors12 |
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| المؤلفون: | Hovelson, Daniel H., McDaniel, Andrew S., Cani, Andi K., Johnson, Bryan, Rhodes, Kate, Williams, Paul D., Bandla, Santhoshi, Bien, Geoffrey, Choppa, Paul, Hyland, Fiona, Gottimukkala, Rajesh, Liu, Guoying, Manivannan, Manimozhi, Schageman, Jeoffrey, Ballesteros-Villagrana, Efren, Grasso, Catherine S., Quist, Michael J., Yadati, Venkata, Amin, Anmol, Siddiqui, Javed, Betz, Bryan L., Knudsen, Karen E., Cooney, Kathleen A., Feng, Felix Y., Roh, Michael H., Nelson, Peter S., Liu, Chia-Jen, Beer, David G., Wyngaard, Peter, Chinnaiyan, Arul M., Sadis, Seth, Rhodes, Daniel R., Tomlins, Scott A. |
| المصدر: | Neoplasia (New York, N.Y.) |
| بيانات النشر: | Neoplasia Press, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Proto-Oncogene Proteins B-raf, NCCN, National Comprehensive Cancer Network, CNAs, copy number alterations, DNA Mutational Analysis, PR, prostate cohort, Article, LU, lung cohort, Proto-Oncogene Proteins p21(ras), OCP, Oncomine Comprehensive Panel, indels, insertions/deletions, SCC, small cell carcinoma, Transcriptional Regulator ERG, Neoplasms, Proto-Oncogene Proteins, Humans, Anaplastic Lymphoma Kinase, QMRS, Quantitative Multiplex Reference Standard, MO, molecular cohort, beta Catenin, Aged, Retrospective Studies, MCR, minimal common region, Serine Endopeptidases, Computational Biology, High-Throughput Nucleotide Sequencing, Receptor Protein-Tyrosine Kinases, PGM, Personal Genome Machine, DNA, Neoplasm, Middle Aged, FFPE, formalin-fixed paraffin-embedded, NGS, next-generation sequencing, ErbB Receptors, GoF, gain-of-function, LoF, loss-of-function, Mutation, Trans-Activators, ras Proteins, AOHC, AcroMetrix Oncology Hotspot Control, TCGA, The Cancer Genome Atlas, Female |
| الوصف: | Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with 95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts. |
| اللغة: | English |
| تدمد: | 1476-5586 1522-8002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::4d12a35876071dc9bfe5d003ea1ccf27Test http://europepmc.org/articles/PMC4415141Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........4d12a35876071dc9bfe5d003ea1ccf27 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765586 15228002 |
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