Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): A hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology Journal Article
| Authors: | Cheng, D. T.; Mitchell, T. N.; Zehir, A.; Shah, R. H.; Benayed, R.; Syed, A.; Chandramohan, R.; Liu, Z. Y.; Won, H. H.; Scott, S. N.; Brannon, A. R.; O Reilly, C.; Sadowska, J.; Casanova, J.; Yannes, A.; Hechtman, J. F.; Yao, J.; Song, W.; Ross, D. S.; Oultache, A.; Dogan, S.; Borsu, L.; Hameed, M.; Nafa, K.; Arcila, M. E.; Ladanyi, M.; Berger, M. F. |
| Article Title: | Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): A hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology |
| Abstract: | The identification of specific genetic alterations as key oncogenic drivers and the development of targeted therapies are together transforming clinical oncology and creating a pressing need for increased breadth and throughput of clinical genotyping. Next-generation sequencing assays allow the efficient and unbiased detection of clinically actionable mutations. To enable precision oncology in patients with solid tumors, we developed Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 341 key cancer genes in formalin-fixed, paraffin-embedded tumors. Barcoded libraries from patient-matched tumor and normal samples were captured, sequenced, and subjected to a custom analysis pipeline to identify somatic mutations. Sensitivity, specificity, reproducibility of MSK-IMPACT were assessed through extensive analytical validation. We tested 284 tumor samples with previously known point mutations and insertions/deletions in 47 exons of 19 cancer genes. All known variants were accurately detected, and there was high reproducibility of inter- and intrarun replicates. The detection limit for low-frequency variants was approximately 2% for hotspot mutations and 5% for nonhotspot mutations. Copy number alterations and structural rearrangements were also reliably detected. MSK-IMPACT profiles oncogenic DNA alterations in clinical solid tumor samples with high accuracy and sensitivity. Paired analysis of tumors and patient-matched normal samples enables unambiguous detection of somatic mutations to guide treatment decisions. © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. |
| Journal Title: | Journal of Molecular Diagnostics |
| Volume: | 17 |
| Issue: | 3 |
| ISSN: | 1525-1578 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2015-05-01 |
| Start Page: | 251 |
| End Page: | 264 |
| Language: | English |
| DOI: | 10.1016/j.jmoldx.2014.12.006 |
| PROVIDER: | scopus |
| PUBMED: | 25801821 |
| PMCID: | PMC5808190 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
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