Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice
Open accessAbstract
Background Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care.Methods We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.Results Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.Conclusions Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
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Targeted multiplexed hotspot panels are already developed and available in CAP-accredited academic and commercial laboratories.
“Targeted multiplexed hotspot panels (e.g., Agena Oncocarta [Agena Bioscience, San Diego, CA], 47 SNaPshot [Applied Biosystems, Foster City, CA], 48 and next-generation sequencing [NGS] panels 49,50 ) have already been developed and are available in College of American Pathologists (CAP)-accredited academic and commercial laboratories.”
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- Authors
- Sequist, L. V., Heist, R. S., Shaw, A. T., Fidias, P., Rosovsky, R., Temel, J. S., Lennes, I. T., Digumarthy, S., Waltman, B. A., Bast, E., Tammireddy, S., Morrissey, L., Muzikansky, A., Goldberg, S. B., Gainor, J., Channick, C. L., Wain, J. C., Gaissert, H., Donahue, D. M., Muniappan, A., Wright, C., Willers, H., Mathisen, D. J., Choi, N. C., Baselga, J., Lynch, T. J., Ellisen, L. W., Mino-Kenudson, M., Lanuti, M., Borger, D. R., Iafrate, A. J., Engelman, J. A., & Dias-Santagata, D.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Yale Cancer Center (US)
- Corresponding author
- Sequist, L.V.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 22
- Issue
- 12
- Pages
- 2616-2624
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC3493130
- OpenAlex
- W2113687561
- Cited by
- 370
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 15 · 2022: 14 · 2021: 29 · 2020: 17 · 2019: 20 · 2018: 20 · 2017: 31 · 2016: 30 · 2015: 44 · 2014: 49 · 2013: 53 · 2012: 34
- FWCI
- 37.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Cancer Institute (P50CA090578)
- 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, multiplex genotyping, snapshots, targeted therapy, ALK rearrangement, KRAS mutation, EGFR mutation, PIK3CA mutation, IDH mutation, CTNNB1 mutation, lung squamous cell carcinoma, multiple primary neoplasms, targeted therapy selection
- MeSH terms
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Clinical Trials as Topic, Diagnostic Tests, Routine, Female, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Biomarkers, Tumor, Molecular Diagnostic Techniques, Kaplan-Meier Estimate, Young Adult, Molecular Targeted Therapy, Multiplex Polymerase Chain Reaction
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