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Germline promoter hypermethylation in BRCA1 and BRCA2 genes is not present in hereditary breast cancer patients

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Abstract

Purpose

Germline promoter hypermethylation of BRCA1 and BRCA2 genes is an alternative event of gene silencing that has not been widely investigated in hereditary breast and ovarian cancer (HBOC) syndrome.

Methods

We analyzed germline BRCA promoter hypermethylation in HBOC patients with and without BRCA mutations and control subjects, using a recently developed BRCA methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay.

Results

Neither the patients tested nor the control subjects showed germline hypermethylation of the BRCA1 and BRCA2 promoter regions analyzed.

Conclusions

Despite the results achieved at somatic levels by other researchers, these were not confirmed in our study at the germline level. Our results show the need to establish more predictive CpG sites in the BRCA promoter regions to optimize the MS-MLPA assay for the detection of germline hypermethylation as an effective pre-screening tool for whole-BRCA genetic analysis in HBOC, because we can not rule out the existence of germline promoter hypermethylation in BRCA.

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Acknowledgements

The genomic analyses were performed at the Centre for Omic Sciences (COS) of the Universitat Rovira i Virgili.

Author information

Author notes

  1. M. Rodríguez-Balada and B. Roig contributed equally to this work.

Authors and Affiliations

  1. Institut d’Oncologia de la Catalunya Sud (IOCS), Hospital Universitari Sant Joan de Reus, IISPV, Universitat Rovira i Virgili, Av. Del Dr. Josep Laporte, 43204, Reus, Spain

    M. Rodríguez-Balada, B. Roig, M. Melé, M. Salvat, J. Borràs & J. Gumà

  2. Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, CIBERSAM, C/Sant Llorenç, Reus, Spain

    L. Martorell

Authors
  1. M. Rodríguez-Balada
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  2. B. Roig
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  3. M. Melé
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  4. M. Salvat
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  5. L. Martorell
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  6. J. Borràs
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  7. J. Gumà
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Corresponding authors

Correspondence to M. Rodríguez-Balada or J. Gumà.

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Conflict of interest

MS-MLPA reagents were made available by MRC-Holland, Amsterdam, the Netherlands. The ME053-X1 BRCA1-BRCA2 probemix was designed by Lilit Atanesyan. MRC-Holland was not involved in the design or analysis of the experiments or in the writing of the manuscript.

Ethical approval

This study was approved by the Ethics Committee of Clinical Research of Sant Joan University Hospital, and written informed consent was obtained from all participants.

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Rodríguez-Balada, M., Roig, B., Melé, M. et al. Germline promoter hypermethylation in BRCA1 and BRCA2 genes is not present in hereditary breast cancer patients. Clin Transl Oncol 20, 1226–1231 (2018). https://doi.org/10.1007/s12094-018-1837-0

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  • DOI: https://doi.org/10.1007/s12094-018-1837-0

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