Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes.
Mounting evidence suggests that aberrant methylation of CpG islands is a major pathway leading to the inactivation of tumor suppressor genes and the development of cancer. Recent studies on colorectal and gastric cancer have defined a CpG island methylator phenotype (CIMP), which involves the targeting of multiple genes by promoter hypermethylation. To determine the role of methylation in ovarian cancer, we have investigated the methylation status of 93 primary ovarian tumors at ten loci using methylation-specific polymerase chain reaction (MSP). Seven of the loci (BRCA1, HIC1, MINT25, MINT31, MLH1, p73 and hTR) were found to be methylated in a significant proportion of the ovarian tumors, and methylation of at least one of these was found in the majority (71%) of samples. Although concurrent methylation of multiple genes was commonly seen, this did not seem to be due to a single CIMP phenotype. Instead the results suggest the presence of at least three groups of tumors, two CIMP-positive groups, each susceptible to methylation of a different subset of genes, and a further group of tumors not susceptible to CpG island methylation, at least at the loci studied.
Strathdee
G
G
Cancer Research Campaign Department of Medical Oncology, CRC Beatson Laboratories, Glasgow University, Glasgow G61 1BD, United Kingdom.
Appleton
K
K
Illand
M
M
Millan
D W
DW
Sargent
J
J
Paul
J
J
Brown
R
R
D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1