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Breast Cancer Research and Treatment

, Volume 151, Issue 2, pp 319–324 | Cite as

Exome sequencing of contralateral breast cancer identifies metastatic disease

  • Daniel KlevebringEmail author
  • Johan Lindberg
  • Julia Rockberg
  • Camilla Hilliges
  • Per Hall
  • Maria Sandberg
  • Kamila Czene
Preclinical study

Abstract

Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.

Keywords

Breast cancer Contralateral Bilateral Recurrence Metastasis 

Notes

Acknowledgments

The authors would like to thank the Science for Life Laboratory Stockholm Application lab for sequencing and Gabriela Prochazka, Anna Westring, Simon Sundling, and Heidi Talvitie for help with library preparation of the samples.

Conflict of interest

The authors have no conflicts of interest.

Supplementary material

10549_2015_3403_MOESM1_ESM.pdf (44 kb)
(PDF 45 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  2. 2.Science for Life LaboratoryStockholmSweden
  3. 3.Department of Oncology-PathologyKarolinska InstitutetStockholmSweden
  4. 4.Department of Clinical PathologyKarolinska University HospitalStockholmSweden
  5. 5.Institute of Environmental MedicineKarolinska InstitutetStockholmSweden

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