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EMSY copy number variation in male breast cancers characterized for BRCA1 and BRCA2 mutations

Breast Cancer Research and Treatment volume 160, pages 181–186 (2016)Cite this article

Abstract

Purpose

Male breast cancer (MBC) is a rare disease that shares some similarities with female breast cancer (FBC). Like FBC, genetic susceptibility to MBC can be referred to mutations in BRCA1 and, particularly, BRCA2 genes. However, only about 10 % of MBCs are caused by BRCA1/2 germ-line mutations, while the largest part are sporadic cancers and may derive from somatic alterations. EMSY, a BRCA2 inactivating gene, emerged as a candidate gene involved in the pathogenesis of sporadic FBC, and its amplification was suggested to be the somatic counterpart of BRCA2 mutations. Considering the relevant role of BRCA2 in MBC, we aimed at investigating the role of EMSY gene copy number variations in male breast tumors.

Methods

EMSY copy number variations were analyzed by quantitative real-time PCR with TaqMan probes in a selected series of 75 MBCs, characterized for BRCA1/2 mutations.

Results

We reported EMSY amplification in 34.7 % of MBCs. A significant association emerged between EMSY amplification and BRCA1/2 mutations (p = 0.03). We identified two amplification subgroups characterized by low and high amplification levels, with BRCA2-related tumors mostly showing low EMSY amplification.

Conclusions

Our results show a high frequency of EMSY amplification in MBC, thus pointing to a role of EMSY in the pathogenesis of this disease. EMSY amplification may be a new feature that might uncover underlying molecular pathways of MBCs and may allow for the identification of MBC subgroups with potential clinical implication for targeted therapeutic approaches.

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Acknowledgments

The authors thank all the individuals who participated in this study and all the institutions and their staff who supported the recruitment of patients and the collection of samples and data. The authors thank L. Pritikin for her precious advices in the preparation of the manuscript.

Funding

This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC IG 16933) to L. O., Fondazione Umberto Veronesi (Annual Post-doctoral Fellowships) to P. R. and Istituto Toscano Tumori (ITT-2010) to D. P.

Author information

Affiliations

  1. Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Anna Sara Navazio, Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli & Laura Ottini

  2. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy

    Ines Zanna, Giovanna Masala & Domenico Palli

  3. Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    Simonetta Bianchi

  4. Molecular Genetics Laboratory, Istituto Tumori “Giovanni Paolo II”, Bari, Italy

    Stefania Tommasi

Authors
  1. Anna Sara Navazio
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  2. Piera Rizzolo
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  3. Valentina Silvestri
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  4. Virginia Valentini
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  5. Veronica Zelli
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  6. Ines Zanna
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  7. Giovanna Masala
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  8. Simonetta Bianchi
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  9. Stefania Tommasi
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  10. Domenico Palli
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  11. Laura Ottini
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Corresponding author

Correspondence to Laura Ottini.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The experiments comply with the current laws of Italy. Informed consent was obtained from all individual participants included in the study. The study was approved by the local ethical committee (Sapienza University of Rome, Protocol 264/12).

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Navazio, A.S., Rizzolo, P., Silvestri, V. et al. EMSY copy number variation in male breast cancers characterized for BRCA1 and BRCA2 mutations. Breast Cancer Res Treat 160, 181–186 (2016). https://doi.org/10.1007/s10549-016-3976-8

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  • DOI: https://doi.org/10.1007/s10549-016-3976-8

Keywords

  • Male breast cancer
  • EMSY
  • Copy number variation
  • BRCA1/2 germ-line mutations