Research Papers:

Comparative genomic analysis of primary tumors and metastases in breast cancer

François Bertucci _, Pascal Finetti, Arnaud Guille, José Adélaïde, Séverine Garnier, Nadine Carbuccia, Audrey Monneur, Emmanuelle Charafe-Jauffret, Anthony Goncalves, Patrice Viens, Daniel Birnbaum and Max Chaffanet

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Oncotarget. 2016; 7:27208-27219. https://doi.org/10.18632/oncotarget.8349

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François Bertucci1,2,3, Pascal Finetti1,*, Arnaud Guille1,*, José Adélaïde1,*, Séverine Garnier1,*, Nadine Carbuccia1, Audrey Monneur1,2, Emmanuelle Charafe-Jauffret1,3,4, Anthony Goncalves2,3, Patrice Viens2,3, Daniel Birnbaum1, Max Chaffanet1

1Département d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France

2Département d’Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France

3Faculté de Médecine, Aix-Marseille Université, Marseille, France

4Département de Biopathologie, CRCM, Institut Paoli-Calmettes, Marseille, France

*These authors contributed equally to this work

Correspondence to:

François Bertucci, e-mail: [email protected]

Keywords: array-CGH, breast cancer, genomics, metastasis, sequencing

Received: January 08, 2016     Accepted: March 14, 2016     Published: March 25, 2016


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.

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