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TIMP3 Promoter Methylation Represents an Epigenetic Marker of BRCA1ness Breast Cancer Tumours

  • Short Communication
  • Published:
Pathology & Oncology Research

Abstract

Tumours presenting BRCAness profile behave more aggressively and are more invasive as a consequence of their complex genetic and epigenetic alterations, caused by impaired fidelity of the DNA repair processes. Methylation of promoter CpG islands represents an alternative mechanism to inactivate DNA repair and tumour suppressor genes. In our study, we analyzed the frequency of methylation changes of 24 tumour suppressor genes and explored their association with BRCAness profile. BRCA1ness profile and aberrant methylation were studied in 233 fresh frozen breast tumour tissues by Multiplex Ligation-dependent Probe Amplification (MLPA) and Methylation Specific (MS)-MLPA methods, respectively. Our analyses revealed that 12.4% of the breast cancer (BC) patients had tumours with a BRCA1ness profile. TIMP3 showed significantly higher (p = 5.8х10−5) methylation frequency in tumours with BRCA1ness, while methylation of APC, GSTP1 and RASSF1 promoters was negatively associated with BRCA1ness (р = 0.0017, р = 0.007 and р = 0.046, respectively). TIMP3 methylation was also associated with triple negative (TN) BC. Furthermore, TN tumours showing BRCA1ness showed stronger association with TIMP3 methylation (p = 0.0008) in comparison to TN tumours without BRCA1ness (p = 0.009). In conclusion, we confirmed that TIMP3 methylation is a marker for TN tumours and furthermore we showed for the first time that TIMP3 promoter methylation is an epigenetic marker of BRCA1ness tumours.

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Acknowledgments

We cordially thank all patients and clinicians who participated in sampling and documentation.

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Authors and Affiliations

  1. Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov”, Macedonian Academy of Sciences and Arts, KrsteMisirkov 2, Skopje, Republic of Macedonia

    Ivana Maleva Kostovska, Milena Jakimovska, Katerina Popovska-Jankovic & Dijana Plaseska-Karanfilska

  2. Clinical Hospital Acibadem Sistina, Skopje, Republic of Macedonia

    Katerina Kubelka-Sabit & Mitko Karagjozov

Authors
  1. Ivana Maleva Kostovska
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  2. Milena Jakimovska
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  3. Katerina Popovska-Jankovic
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  4. Katerina Kubelka-Sabit
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  5. Mitko Karagjozov
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  6. Dijana Plaseska-Karanfilska
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Contributions

All co-authors contributed to the conception and design, analysis and interpretation of data. IMK and DPK drafted the article and DPK is a guarantor for the article.

All co-authors have seen and agree with the content and conclusions in the submitted version of the article, confirm that the work has not been published/submitted elsewhere and agree with submission manuscript.

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Correspondence to Dijana Plaseska-Karanfilska.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Maleva Kostovska, I., Jakimovska, M., Popovska-Jankovic, K. et al. TIMP3 Promoter Methylation Represents an Epigenetic Marker of BRCA1ness Breast Cancer Tumours. Pathol. Oncol. Res. 24, 937–940 (2018). https://doi.org/10.1007/s12253-018-0398-4

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  • DOI: https://doi.org/10.1007/s12253-018-0398-4

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