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


Yandim C., KARAKÜLAH G.

CANCER GENETICS, vol.239, pp.36-45, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 239
  • Publication Date: 2019
  • Doi Number: 10.1016/j.cancergen.2019.09.002
  • Journal Name: CANCER GENETICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.36-45
  • Keywords: Breast cancer, Repetitive DNA, Survival, Transcriptome analysis, Bioinformatics, COMPREHENSIVE MOLECULAR PORTRAITS, TRANSPOSABLE ELEMENTS, GENE-EXPRESSION, ENDOGENOUS RETROVIRUSES, BREAST, HETEROCHROMATIN, TRANSCRIPTION, PROMOTERS, LANDSCAPE, DISEASES
  • Dokuz Eylül University Affiliated: Yes

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. (C) 2019 Elsevier Inc. All rights reserved.