Genome-wide methylation profiles in monozygotic twins with discordance for ovarian carcinoma

Erdogan O. S., Tuncer S. B., Kilic S., Odemis D. A., Turkcan G. K., Celik B., ...Daha Fazla

ONCOLOGY LETTERS, cilt.20, sa.6, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.3892/ol.2020.12221
  • Dergi Adı: ONCOLOGY LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE
  • Anahtar Kelimeler: monozygotic twins, whole-genome DNA methylation, epithelial ovarian cancer, BRCA1 gene mutation, epigenetics, DNA METHYLATION, EPIGENETIC DIFFERENCES, BREAST-CANCER, RISK, EPIGENOMICS, PROTEIN, FAMILY
  • İstanbul Üniversitesi Adresli: Evet

Özet

Ovarian cancer is a disease that is generally diagnosed at an advanced stage, and has poor survival. Monozygotic (MZ) twins are considered to be good research models for investigating the epigenetic changes associated with diseases. In the present study, the involvement of epigenetic mechanisms in ovarian cancer etiology were evaluated using the MZ twin model. Whole-genome methylation patterns were investigated in a BRCA1 gene mutation-carrying family comprising MZ twins, only one of whom had ovarian cancer, and other healthy siblings. Whole-genome methylation patterns were assessed in peripheral blood DNA using Infinium MethylationEPIC BeadChips on an Illumina iScan device. The hypermethylated and hypomethylated genes were detected between cases and controls in four different comparison groups in order to evaluate the differences in methylation levels according to cancer diagnosis and BRCA mutation status. The obtained results showed that the differential methylations in 12 different genes, namely PR/SET domain 6, cytochrome B5 reductase 4, ZNF714, OR52M1, SEMA4D, CHD1L, CAPZB, clustered mitochondria homolog, RB-binding protein 7, chromatin repair factor, ankyrin repeat domain 23, RIB43A domain with coiled-coils 1 and C6orf227, were associated with ovarian cancer. Biological functional analysis of the genes detected in the study using the PANTHER classification system revealed that they have roles in biological processes including 'biologic adhesion', 'regulation', 'cellular components organization', 'biogenesis', 'immune system functioning', 'metabolic functioning' and 'localization'. Overall, the present study suggested that epigenetic differences, such as methylation status, could be used as a non-invasive biological markers for the early diagnosis and follow-up of ovarian cancer.