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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MSK Authors
  1. Meera Hameed
    136 Hameed
  2. Khedoudja Nafa
    181 Nafa
  3. Jinjuan Yao
    23 Yao
  4. Marc Ladanyi
    864 Ladanyi
  5. Snjezana Dogan
    86 Dogan
  6. Ahmet Zehir
    149 Zehir
  7. Michael Forman Berger
    380 Berger
  8. Maria Eugenia Arcila
    336 Arcila
  9. Dara Stacy Ross
    42 Ross
  10. Helen Hyeong-Eun Won
    79 Won
  11. Angela Rose Brannon
    31 Brannon
  12. Ronak Hasmukh Shah
    43 Shah
  13. Donavan Tai Suan Cheng
    51 Cheng
  14. Sasinya Neka Scott
    66 Scott
  15. Aijazuddin Syed
    20 Syed
  16. Wei Song
    4 Song
  17. Rym Benayed
    68 Benayed
  18. Zhen Yu   Liu
    3 Liu