Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers

Abstract

Aberrant methylation of multiple promoter CpG islands could be related to the biology of ovarian tumors and its determination could help to improve treatment strategies. DNA methylation profiling was performed using the Methylation Ligation-dependent Macroarray (MLM), an array-based analysis. Promoter regions of 41 genes were analyzed in 102 ovarian tumors and 17 normal ovarian samples. An average of 29% of hypermethylated promoter genes was observed in normal ovarian tissues. This percentage increased slightly in serous, endometrioid, and mucinous carcinomas (32%, 34%, and 45%, respectively), but decreased in germ cell tumors (20%). Ovarian tumors had methylation profiles that were more heterogeneous than other epithelial cancers. Unsupervised hierarchical clustering identified four groups that are very close to the histological subtypes of ovarian tumors. Aberrant methylation of three genes (BRCA1, MGMT, and MLH1), playing important roles in the different DNA repair mechanisms, were dependent on the tumor subtype and represent powerful biomarkers for precision therapy. Furthermore, a promising relationship between hypermethylation of MGMT, OSMR, ESR1, and FOXL2 and overall survival was observed. Our study of DNA methylation profiling indicates that the different histotypes of ovarian cancer should be treated as separate diseases both clinically and in research for the development of targeted therapies.

Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness

“…Epigenetic modulations of ADME genes and drug targets may be important determinant of responses to drugs [120]. Especially, epigenetics can play an important role in the acquired resistance to chemotherapy in cancer patients and epigenetic biomarkers may predict the outcomes of chemotherapy [121,122]. In addition to drug-gene interactions, drug-gene-drug interactions may also cause differences in drug response and should be considered during prescribing drugs [123,124].…”

Molecular biomarkers for early detection and prevention of ovarian cancer—A gateway for good prognosis: A narrative review

“…On the other hand, in a CpG island when a given stretch of cytosines in the promoter region of a gene is not methylated, in this case, it would be 'hypomethylated (not silenced by methylation). [ 41 ]…”

Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

“…Gene selection is also important for the study of ovarian cancer. Whilst Losi et al [16] and Choi et al [17] listed genes involved in cancer in general those epigenetically modifiable promoter genes relevant to ovarian cancer are given in Table 1. Genes involved in cisplatin/carboplatin resistance/sensitization of ovarian cancer are presented in Table 2.…”