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Dysregulated expression of repetitive DNA in ER+/HER2- breast cancer

  • Cihangir Yandım
    Affiliations
    İzmir University of Economics, Faculty of Engineering, Department of Genetics and Bioengineering, 35330, Balçova, İzmir, Turkey

    İzmir Biomedicine and Genome Center (IBG), Dokuz Eylül University Health Campus, 35340, İnciraltı, İzmir, Turkey
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  • Gökhan Karakülah
    Correspondence
    Corresponding author.
    Affiliations
    İzmir Biomedicine and Genome Center (IBG), Dokuz Eylül University Health Campus, 35340, İnciraltı, İzmir, Turkey

    İzmir International Biomedicine and Genome Institute (iBG-İzmir), Dokuz Eylül University, 35340, İnciraltı, İzmir, Turkey
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Published:September 06, 2019DOI:https://doi.org/10.1016/j.cancergen.2019.09.002

      Highlights

      • Expressions of 56 repetitive DNA elements comprising all main repeat classes are significantly dysregulated in ER+/HER2- breast cancer tumours.
      • HERVKC4-int and HERV1_LTRc were the most upregulated transposons, and their expressions correlate with that of the estrogen receptor gene ESR1.
      • REP522 and D20S16 were the most upregulated satellites and their expressions correlate with that of key breast cancer pathway (e.g. BRCA1, BRCA2, AKT1, MTOR, KRAS) as well as many survival genes significantly.
      • Additional repeat elements (e.g. members of MER family) are enriched within the promoters of genes that are dysregulated in breast cancer.

      Abstract

      Limited studies on breast cancer indicated pathogenic changes in the expressions of some repeat elements. A global analysis was much needed within this context to distinguish the most significant repeats from more than a thousand repeat motifs. Utilising a previously presented RNA-seq dataset, we studied expression changes of all repeats in ER+/HER2- human breast tumour samples obtained from 22 patients in comparison to matched normal tissues. Fifty six (56) repeat subtypes including satellites and transposons were found to be differentially expressed and most of them were novel for breast cancer. HERVKC4-int and HERV1_LTRc, whose expressions correlated well with that of the estrogen receptor gene ESR1, were upregulated at the highest level. REP522 and D20S16 satellites were also significantly upregulated along with insignificant increases in the expressions of other satellites including HSATI and BSR/beta. Interestingly, expressions of REP522 and D20S16 correlated with many key breast cancer pathway (e.g. BRCA1, BRCA2, AKT1, MTOR, KRAS) and survival genes; possibly highlighting their importance in the carcinogenesis of breast. Additional differentially expressed elements such as L1P and various MER transposons also exhibited a similar pattern. Finally, our repeat enrichment analysis on the promoters of differentially expressed genes revealed further links between additional repeats and nearby genes.

      Keywords

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