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A platform for rapid detection of multiple oncogenic mutations with relevance to targeted therapy in non-small-cell lung cancer.
Open accessAbstract
The identification of somatically acquired tumor mutations is increasingly important in the clinical management of cancer because the sensitivity of targeted drugs is related to the genetic makeup of individual tumors. Thus, mutational profiles of tumors can help prioritize anticancer therapy. We report herein the development and validation of two multiplexed assays designed to detect in DNA from FFPE tissue more than 40 recurrent mutations in nine genes relevant to existing and emerging targeted therapies in lung cancer. The platform involves two methods: a screen (SNaPshot) based on multiplex PCR, primer extension, and capillary electrophoresis that was designed to assess for 38 somatic mutations in eight genes (AKT1, BRAF, EGFR, KRAS, MEK1, NRAS, PIK3CA, and PTEN) and a PCR-based sizing assay that assesses for EGFR exon 19 deletions, EGFR exon 20 insertions, and HER2 exon 20 insertions. Both the SNaPshot and sizing assays can be performed rapidly, with minimal amounts of genetic material. Compared with direct sequencing, in which mutant DNA needs to compose 25% or more of the total DNA to easily detect a mutation, the SNaPshot and sizing assays can detect mutations in samples in which mutant DNA composes 1.56% to 12.5% and 1.56% to 6.25% of the total DNA, respectively. These robust, reliable, and relatively inexpensive assays should help accelerate adoption of a genotype-driven approach in the treatment of lung cancer.
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“Indeed, pre-clinical reports have suggested that “third generation” agents can induce switching to multiple signaling mechanisms that bypass EGFR dependency such as ERK and AKT pathways (35, 61, 62).”
From AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer (2014) · cites this paper as [61]
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Flagged first, then by citations
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- Pratilas, 2008, Genetic predictors of MEK dependence in non-small cell lung cancer, Cancer Res, 68, 9375, 10.1158/0008-5472.CAN-08-2223 · DOI
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“exon19 del 103 (10) [9-12] 68 (9) [7-12]”
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Metadata
- Authors
- Su, Z., Dias-Santagata, D., Duke, M., Hutchinson, K., Lin, Y.-L., Borger, D. R., Chung, C. H., Massion, P. P., Vnencak-Jones, C. L., Iafrate, A. J., & Pao, W.
- Affiliations
- Vanderbilt University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Pao, William
- ORCID
- Venue
- The Journal of Molecular Diagnostics
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 13
- Issue
- 1
- Pages
- 74-84
- ISSN
- 1525-1578 (ISSN-L)
- PMC
- PMC3070558
- OpenAlex
- W2033780390
- Cited by
- 176
- References
- 36
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 10 · 2016: 21 · 2015: 29 · 2014: 32 · 2013: 25 · 2012: 23
- FWCI
- 23.94
- 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
- NIH/National Cancer Institute (R01 CA121210, P01 CA129243, U54 CA143798, CA102353, RC2-CA148394-01)
- VICC Specialized Program of Research Excellence in Lung Cancer (CA90949)
- Vanderbilt-Ingram Cancer Center Core (CA68485)
- V Foundation
- TJ Martell Foundation
- Kleberg Foundation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- non-small cell lung cancer, somatic mutations, targeted therapy, snapshots, EGFR exon 19 deletion, EGFR exon 20 insertion, HER2 exon 20 insertion, AKT1, BRAF, KRAS, MEK1, NRAS, PIK3CA, PTEN, formalin-fixed paraffin-embedded tissue
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, DNA, Neoplasm, Genetic Testing, Humans, Lung Neoplasms, Mutation, Reproducibility of Results, Cell Line, Tumor, High-Throughput Nucleotide Sequencing
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