[Hypermethylation of fragile histidine triad gene and 3p14 allelic deletion in ovarian carcinomas].
OBJECTIVE
The FHIT (fragile histidine triad) is a candidate tumor suppressor gene (TSG) located on chromosome 3p14.2. Hypermethylation and loss of heterozygosity (LOH) are major mechanisms in the inactivation of tumor suppressor genes. In this study, the methylation status of FHIT and LOH of 3p14 in 61 cases of human sporadic ovary carcinomas were investigated.


METHODS
Sixty-one primary ovary carcinomas and 10 borderline ovarian tumors were analyzed with methylation specific PCR (MSP) to detect the CpG island methylation status in the FHIT promoter region. In addition, 45 cases of ovary carcinomas and their corresponding non-tumor ovary tissues were investigated with D3S1287 microsatellite polymorphic marker for LOH.


RESULTS
Hypermethylation of FHIT gene was observed in 39.3% (24/61) of ovarian carcinomas. The frequencies of hypermethylation in serous ovarian carcinoma, mucinous ovarian carcinoma, endometrioid ovarian carcinoma and ovary borderline tumor were 45.2% (19/42), 14.3% (1/7), 33.3% (4/12) and 60.0% (6/10), respectively. Ten of twenty-three (43.5%) informative tumors showed LOH and 6 of 18 (33.3%) informative cases showed homozygous deletions. The status of FHIT methylation was not associated with clinical stage and differentiation grade, there was no significant difference between the malignant and borderline tumors.


CONCLUSIONS
Hypermethylation and allelic deletion of FHIT are frequent events in ovarian carcinomas and are important mechanisms for the loss of expression of this gene.
Hong
Fan-zhen
FZ
Department of Gynaecology, Qilu Hospital of Shandong University, Jinan 250012, China.
Wang
Bo
B
Li
Hiu-Ming
HM
Liew
Choong-Tsek
CT
D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002893:Chromosomes, Human, Pair 3; D018899:CpG Islands; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase