RGD Reference Report - Multiple promoters of catechol-O-methyltransferase gene are selectively inactivated by CpG hypermethylation in endometrial cancer. - Rat Genome Database

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Multiple promoters of catechol-O-methyltransferase gene are selectively inactivated by CpG hypermethylation in endometrial cancer.

Authors: Sasaki, M  Kaneuchi, M  Sakuragi, N  Dahiya, R 
Citation: Sasaki M, etal., Cancer Res. 2003 Jun 15;63(12):3101-6.
RGD ID: 2289723
Pubmed: PMID:12810635   (View Abstract at PubMed)

Catechol-O-methyltransferase (COMT) plays an important role in estrogen-induced cancers because COMT inactivates catechol estrogens that have cancer-promoting activities. Two promoters control the expression of human COMT isoforms: membrane-bound COMT (MB-COMT) and soluble COMT (S-COMT). We hypothesize that inactivation of MB-COMT and S-COMT is important in understanding the pathogenesis of endometrial cancer. To test this hypothesis, we investigated the methylation status and expression of two COMT isoforms in 4 endometrial cancer cell lines, 60 endometrial cancer tissues, 10 normal endometrium tissues from normal healthy controls, and 32 pairs of cancerous and normal endometrial samples from the same patients using methylation-specific PCR, methylation-specific sequencing, reverse transcription-PCR, and 5'-rapid amplification of cDNA ends. The results of this study clearly demonstrate that MB-COMT was inactivated and methylated, although S-COMT was activated and unmethylated in all endometrial cancer cell lines. The 5-aza-2'-deoxycytidine treatment restored MB-COMT expression in all cell lines. The promoter for MB-COMT was methylated in 47 of 60 cancer tissues but was unmethylated in endometrial tissues from cases without cancer. The promoter for S-COMT was unmethylated in all endometrial cancerous and normal tissues. The CpG methylation density at the MB-COMT promoter was significantly higher in cancer tissues (a mean of 79.1% of the 19 CpG sites; range, 69-94%) than in adjacent normal tissues (a mean of 8.7% of the 19 CpG sites; range, 3-14%). In summary, these findings demonstrate that methylation of multiple promoters of the COMT gene can selectively inactivate MB-COMT and may contribute to endometrial carcinogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial cancer  IDA 2289723DNA:hypermethylation:promoterRGD 
endometrial cancer  ISOCOMT (Homo sapiens)2289723; 2289723DNA:hypermethylation:promoterRGD 

Objects Annotated

Genes (Rattus norvegicus)
Comt  (catechol-O-methyltransferase)

Genes (Mus musculus)
Comt  (catechol-O-methyltransferase)

Genes (Homo sapiens)
COMT  (catechol-O-methyltransferase)


Additional Information