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Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer.
J Clin Oncol 2013; 31(17):2167-72JC

Abstract

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.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23630207

Citation

Vignot, Stéphane, et al. "Next-generation Sequencing Reveals High Concordance of Recurrent Somatic Alterations Between Primary Tumor and Metastases From Patients With Non-small-cell Lung Cancer." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 31, no. 17, 2013, pp. 2167-72.
Vignot S, Frampton GM, Soria JC, et al. Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. J Clin Oncol. 2013;31(17):2167-72.
Vignot, S., Frampton, G. M., Soria, J. C., Yelensky, R., Commo, F., Brambilla, C., ... Brambilla, E. (2013). Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 31(17), pp. 2167-72. doi:10.1200/JCO.2012.47.7737.
Vignot S, et al. Next-generation Sequencing Reveals High Concordance of Recurrent Somatic Alterations Between Primary Tumor and Metastases From Patients With Non-small-cell Lung Cancer. J Clin Oncol. 2013 Jun 10;31(17):2167-72. PubMed PMID: 23630207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. AU - Vignot,Stéphane, AU - Frampton,Garrett M, AU - Soria,Jean-Charles, AU - Yelensky,Roman, AU - Commo,Frédéric, AU - Brambilla,Christian, AU - Palmer,Gary, AU - Moro-Sibilot,Denis, AU - Ross,Jeffrey S, AU - Cronin,Maureen T, AU - André,Fabrice, AU - Stephens,Philip J, AU - Lazar,Vladimir, AU - Miller,Vincent A, AU - Brambilla,Elisabeth, Y1 - 2013/04/29/ PY - 2013/5/1/entrez PY - 2013/5/1/pubmed PY - 2013/12/16/medline SP - 2167 EP - 72 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 31 IS - 17 N2 - 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. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/23630207/Next_generation_sequencing_reveals_high_concordance_of_recurrent_somatic_alterations_between_primary_tumor_and_metastases_from_patients_with_non_small_cell_lung_cancer_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2012.47.7737?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -