Tags

Type your tag names separated by a space and hit enter

Comparative genomic analysis of primary tumors and metastases in breast cancer.
Oncotarget 2016; 7(19):27208-19O

Abstract

Personalized medicine uses genomic information for selecting therapy in patients with metastatic cancer. An issue is the optimal tissue source (primary tumor or metastasis) for testing. We compared the DNA copy number and mutational profiles of primary breast cancers and paired metastases from 23 patients using whole-genome array-comparative genomic hybridization and next-generation sequencing of 365 "cancer-associated" genes. Primary tumors and metastases harbored copy number alterations (CNAs) and mutations common in breast cancer and showed concordant profiles. The global concordance regarding CNAs was shown by clustering and correlation matrix, which showed that each metastasis correlated more strongly with its paired tumor than with other samples. Genes with recurrent amplifications in breast cancer showed 100% (ERBB2, FGFR1), 96% (CCND1), and 88% (MYC) concordance for the amplified/non-amplified status. Among all samples, 499 mutations were identified, including 39 recurrent (AKT1, ERBB2, PIK3CA, TP53) and 460 non-recurrent variants. The tumors/metastases concordance of variants was 75%, higher for recurrent (92%) than for non-recurrent (73%) variants. Further mutational discordance came from very different variant allele frequencies for some variants. We showed that the chosen targeted therapy in two clinical trials of personalized medicine would be concordant in all but one patient (96%) when based on the molecular profiling of tumor and paired metastasis. Our results suggest that the genotyping of primary tumor may be acceptable to guide systemic treatment if the metastatic sample is not obtainable. However, given the rare but potentially relevant divergences for some actionable driver genes, the profiling of metastatic sample is recommended.

Authors+Show Affiliations

Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France. Département d'Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France. Faculté de Médecine, Aix-Marseille Université, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France. Département d'Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France. Faculté de Médecine, Aix-Marseille Université, Marseille, France. Département de Biopathologie, CRCM, Institut Paoli-Calmettes, Marseille, France.Département d'Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France. Faculté de Médecine, Aix-Marseille Université, Marseille, France.Département d'Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France. Faculté de Médecine, Aix-Marseille Université, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27028851

Citation

Bertucci, François, et al. "Comparative Genomic Analysis of Primary Tumors and Metastases in Breast Cancer." Oncotarget, vol. 7, no. 19, 2016, pp. 27208-19.
Bertucci F, Finetti P, Guille A, et al. Comparative genomic analysis of primary tumors and metastases in breast cancer. Oncotarget. 2016;7(19):27208-19.
Bertucci, F., Finetti, P., Guille, A., Adélaïde, J., Garnier, S., Carbuccia, N., ... Chaffanet, M. (2016). Comparative genomic analysis of primary tumors and metastases in breast cancer. Oncotarget, 7(19), pp. 27208-19. doi:10.18632/oncotarget.8349.
Bertucci F, et al. Comparative Genomic Analysis of Primary Tumors and Metastases in Breast Cancer. Oncotarget. 2016 May 10;7(19):27208-19. PubMed PMID: 27028851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative genomic analysis of primary tumors and metastases in breast cancer. AU - Bertucci,François, AU - Finetti,Pascal, AU - Guille,Arnaud, AU - Adélaïde,José, AU - Garnier,Séverine, AU - Carbuccia,Nadine, AU - Monneur,Audrey, AU - Charafe-Jauffret,Emmanuelle, AU - Goncalves,Anthony, AU - Viens,Patrice, AU - Birnbaum,Daniel, AU - Chaffanet,Max, PY - 2016/01/08/received PY - 2016/03/14/accepted PY - 2016/3/31/entrez PY - 2016/3/31/pubmed PY - 2017/12/12/medline KW - array-CGH KW - breast cancer KW - genomics KW - metastasis KW - sequencing SP - 27208 EP - 19 JF - Oncotarget JO - Oncotarget VL - 7 IS - 19 N2 - Personalized medicine uses genomic information for selecting therapy in patients with metastatic cancer. An issue is the optimal tissue source (primary tumor or metastasis) for testing. We compared the DNA copy number and mutational profiles of primary breast cancers and paired metastases from 23 patients using whole-genome array-comparative genomic hybridization and next-generation sequencing of 365 "cancer-associated" genes. Primary tumors and metastases harbored copy number alterations (CNAs) and mutations common in breast cancer and showed concordant profiles. The global concordance regarding CNAs was shown by clustering and correlation matrix, which showed that each metastasis correlated more strongly with its paired tumor than with other samples. Genes with recurrent amplifications in breast cancer showed 100% (ERBB2, FGFR1), 96% (CCND1), and 88% (MYC) concordance for the amplified/non-amplified status. Among all samples, 499 mutations were identified, including 39 recurrent (AKT1, ERBB2, PIK3CA, TP53) and 460 non-recurrent variants. The tumors/metastases concordance of variants was 75%, higher for recurrent (92%) than for non-recurrent (73%) variants. Further mutational discordance came from very different variant allele frequencies for some variants. We showed that the chosen targeted therapy in two clinical trials of personalized medicine would be concordant in all but one patient (96%) when based on the molecular profiling of tumor and paired metastasis. Our results suggest that the genotyping of primary tumor may be acceptable to guide systemic treatment if the metastatic sample is not obtainable. However, given the rare but potentially relevant divergences for some actionable driver genes, the profiling of metastatic sample is recommended. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27028851/Comparative_genomic_analysis_of_primary_tumors_and_metastases_in_breast_cancer_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=8349 DB - PRIME DP - Unbound Medicine ER -