Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer
Open accessAbstract
PURPOSE: Characterization of the genomic changes that drive an individual patient's disease is critical in management of many cancers. In patients with non-small-cell lung cancer (NSCLC), obtaining tumor samples of sufficient size for genomic profiling on recurrence is often challenging. We undertook this study to compare genomic alterations identified in archived primary tumors from patients with NSCLC with those identified in metachronous or synchronous metastases. PATIENTS AND METHODS: Primary and matched metastatic tumor pairs from 15 patients were analyzed by using a targeted next-generation sequencing assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. RESULTS: Among 30 tumors, 311 genomic alterations were identified of which 63 were known recurrent (32 in primary tumor, 31 in metastasis) and 248 were nonrecurrent (likely passenger). TP53 mutations were the most frequently observed recurrent alterations (12 patients). Tumors harbored two or more (maximum four) recurrent alterations in 10 patients. Comparative analysis of recurrent alterations between primary tumor and matched metastasis revealed a concordance rate of 94% compared with 63% for likely passenger alterations. CONCLUSION: This high concordance suggests that for the purposes of genomic profiling, use of archived primary tumor can identify the key recurrent somatic alterations present in matched NSCLC metastases and may provide much of the relevant genomic information required to guide treatment on recurrence.
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Discordance in molecular status between primary and metastatic sites may be linked to tumor heterogeneity between sites.
“A further consideration is discordance in molecular status between primary and metastatic sites, 45,46 which could be associated with tumor heterogeneity between the different sites of involvement.”
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- Authors
- Vignot, S., Frampton, G. M., Soria, J.-C., Yelensky, R., Commo, F., Brambilla, C., Palmer, G., Moro-Sibilot, D., Ross, J. S., Cronin, M. T., André, F., Stephens, P. J., Lazar, V., Miller, V. A., & Brambilla, E.
- Affiliations
- Inserm (FR)
- Stéphane Vignot, Jean-Charles Soria, Frédéric Commo, and Fabrice André, Institut National de la Santé et de la Recherche Médicale (INSERM) U981; Vladimir Lazar, Unité de Génomique Fonctionnelle, Institut Gustave Roussy, Villejuif; Christian Brambilla, Denis Moro-Sibilot, and Elisabeth Brambilla, Centre Hospitalier Universitaire Albert Michallon, INSERM U823, Grenoble, France; Garrett M. Frampton, Roman Yelensky, Gary Palmer, Jeffrey S. Ross, Maureen T. Cronin, Philip J. Stephens, Vincent A. Miller,...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2013-06-10
- Volume
- 31
- Issue
- 17
- Pages
- 2167-2172
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2153800888
- Cited by
- 175
- References
- 24
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 16 · 2020: 11 · 2019: 13 · 2018: 13 · 2017: 19 · 2016: 23 · 2015: 27 · 2014: 25 · 2013: 9
- FWCI
- 22.76
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (cc-by)
- Funders
- European Commission (258677)
- Institut National Du Cancer
- National Cancer Institute
- 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 alterations, metastasis, primary tumor, metachronous metastasis, synchronous metastases, tumor genomic profiling, TP53 mutation, concordance, targeted next-generation sequencing
- MeSH terms
- Adult, Aged, Aged, 80 and over, Base Sequence, Carcinoma, Non-Small-Cell Lung, DNA, Neoplasm, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Metastasis, DNA Copy Number Variations
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