Multiple Methylator Phenotypes Involving Tumor Suppressor Genes in Ovarian Cancers

Ryu, Hyo Chung; Cho, Chi Heum; Kwon, Sang Hoon; Park, Joon Cheol; Seo, Min Ae; Chung, Sun Wok; Rhee, Jeong Ho; Kim, Jong In; Yoon, Sung Do; Cha, Soon Do

Abstract

OBJECTIVE
Recent evidence suggests that aberrant methylation of CpG islands is a major pathway leading to the inactivation of tumor suppressor genes and development of cancer. The purpose of this study was to detect the methylation in ovarian cancer.
METHODS
Recent studies on colorectal and breast cancer have defined a CpG island methylator phenotype, which involves the targeting of multiple genes by promotor hypermethylation. Little is currently known about the role of methylation in ovarian cancer. To detect the methylation in ovarian cancer, we have investigated the methylation status of 13 primary ovarian cancers at six genes using methylation specific polymerase chain reaction compared with 7 normal ovaries.
RESULTS
Six of tumor suppressor genes (p15, p16, p21, p73, BRCA1, and hMLH1) were evaluated to see the methylation status. Methylation of p15, p21, p73, and hMLH1 did not detect in ovarian cancers compared with normal ovaries. Ten of 13 ovarian cancers showed methylation of p16 gene and all normal ovaries showed hypermethylation. The BRCA1 gene was methylated in 11 (85%) of 13 ovarian cancers, 4 (57%) of 7 normal ovaries.
CONCLUSION
Methylation of the BRCA1 gene is common alteration in ovarian cancers, and may paly a part of role in pathogenesis of ovarian cancer.