Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)
Open accessAbstract
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.
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Exome sequencing of sorted cKit+ Lymph- Ery- HSPCs and paired tail tissue using the MSK-IMPACT mouse panel of 578 cancer-related genes showed evidence for expansion of clonal cell populations in all leukemic compound mutant mice tested.
“Exome sequencing of sorted cKit+ Lymph– Ery– HSPCs and paired tail tissue specimen using the Memorial Sloan Kettering Cancer Center's Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) mouse panel of 578 cancer-related genes (31) showed evidence for expansion of clonal cell populations in all leukemic compound mutant mice tested (Supplementary Tables S2 and S3).”
From PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i> -Deficient Hematopoiesis from Malignant Transformation (2022) · cites this paper as [31]
The Panel Design and Target Region Coverage section identifies MSK-IMPACT as a targeted sequencing assay for cancer-related genes, supporting the citation's identification of the method. It describes a 341-gene panel, however, not a 578-gene mouse panel. The cited paper does not report the mouse HSPC sequencing or clonal-expansion result; the citing sentence points to its own supplementary tables for that result. (LLM, conf=0.88)
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Self-citationMundi, P. S., Dela Cruz, F. S., Grunn, A., Diolaiti, D., Mauguen, A., Rainey, A. R., Guillan, K. C., Siddiquee, A., You, D., Realubit, R., et al. (2021) · doi:10.1101/2021.10.03.462951 · Cited by 51 · see citing works
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“Exome sequencing of sorted cKit+ Lymph– Ery– HSPCs and paired tail tissue specimen using the Memorial Sloan Kettering Cancer Center’s Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) mouse panel of 578 cancerrelated genes (31) showed evidence for expansion of clonal cell populations in all leuke…”
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Self-citationA microglia clonal inflammatory disorder in Alzheimer’s disease
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PRISM2: Unlocking Multi-Modal General Pathology AI with Clinical Dialogue
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- 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.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Berger, Michael F.
- ORCID
- Venue
- The Journal of Molecular Diagnostics
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 17
- Issue
- 3
- Pages
- 251-264
- ISSN
- 1525-1578 (ISSN-L)
- PMC
- PMC5808190
- OpenAlex
- W223909586
- Cited by
- 2,119
- References
- 8
- Citations by year
- 2026: 139 · 2025: 225 · 2024: 246 · 2023: 188 · 2022: 252 · 2021: 240 · 2020: 231 · 2019: 176 · 2018: 151 · 2017: 126 · 2016: 101 · 2015: 40 · 2014: 3
- FWCI
- 46.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Molecular Diagnostics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Pathology, Memorial Sloan Kettering Cancer Center
- Farmer Family Foundation
- Geoffrey Beene Cancer Research Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- MSK-IMPACT, somatic mutations, hybridization capture sequencing, precision oncology, solid tumors, formalin-fixed paraffin-embedded tissue, targeted deep sequencing, copy number alterations, structural rearrangement, low-frequency variant detection, analytical method validation, targeted therapy
- MeSH terms
- DNA, DNA Mutational Analysis, Genotype, Humans, Mutation, Neoplasms, Reproducibility of Results, Paraffin Embedding, High-Throughput Nucleotide Sequencing
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