Frequent aberrant methylation of the imprinted IGF2/H19 locus and LINE1 hypomethylation in ovarian carcinoma.
Epigenetic alteration of tumor-related genes through changes of DNA methylation is a hallmark for carcinogenesis and aberrant DNA methylation modulates the activity of tumor suppressor genes, imprinted genes and repetitive elements. In ovarian carcinoma, frequent loss of imprinting or aberrant methylation of repetitive elements were reported, however, combined analysis were not performed. We analyzed the aberrant methylation of a differentially methylated region (DMR0) and a CTCF binding site of the IGF2-H19 locus and methylation of LINE1 and Satellite 2 in 22 primary ovarian carcinomas (OC) and controls by a quantitative bisulfite restriction analysis (QUBRA). In 91% of OC, a significant hypomethylation of DMR0 was found compared to controls (p<0.05). In 77% of OC, a hypermethylation of a CTCF binding site was found (p<0.05). A combined hypomethylation of DMR0 and hypermethylation of the CTCF binding was observed in 73% of OC. Hypomethylation of LINE1 and Satellite 2 was detected in 100 and 23% of OC, respectively. In summary, we found frequent combined aberrant methylation of the IGF2-H19 locus and LINE1 in the vast majority of OC, suggesting that these changes are important events in tumorigenesis.
Dammann
Reinhard H
RH
Institute for Genetics, Justus Liebig University Giessen, Heinrich-Buff-Ring 58-62, D-35392, Giessen, Germany. reinhard.dammann@gen.bio.uni-giessen.de
Kirsch
Sebastian
S
Schagdarsurengin
Undraga
U
Dansranjavin
Temuujin
T
Gradhand
Elise
E
Schmitt
Wolfgang D
WD
Hauptmann
Steffen
S
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
D014408:Biomarkers, Tumor; D017931:DNA Primers; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II