NEW YORK (Reuters Health) - Hypermethylation of genes associated with ovarian cancer can be detected in blood, peritoneal fluid or tissue samples, according to researchers at the Fox Chase Cancer Center. They say, “Analysis of tumor-specific hypermethylation in serum DNA may enhance early detection of ovarian cancer.”
In the September 15th issue of Cancer Research, senior author Dr. Paul Cairns and his colleagues at in Philadelphia, Pennsylvania, explain that the tumor suppressor genes BRCA1 and RASSF1A -- both of which are strongly associated with ovarian cancer -- are unmethylated in normal cells but silenced by hypermethylation in tumors.
Using methylation-specific polymerase chain reaction, the researchers analyzed blood samples and peritoneal fluid DNA from 50 women with ovarian or primary peritoneal cancer, blood samples from 20 healthy age-matched women, normal ovary tissue from 10 women, and tissue, blood and peritoneal fluid samples from 10 women with benign ovarian cysts.
Hypermethylation of one or both genes was found in 68% of ovarian tumor DNA samples. Furthermore, it was observed in all histologic cell types, grades and stages of tumor.
Although the remaining 16 tumor samples did not show hypermethylation for RASSF1A or BRCA1, they did show hypermethylation of the tumor suppressor genes APC, p14, p16 and death-associated protein kinases, “which extended diagnostic coverage to 100%,” the researchers found.
“An identical pattern of gene hypermethylation was found in the matched serum DNA from 41 of 50 patients (82% sensitivity), including 13 of 17 cases of stage I disease,” Dr. Cairns and colleagues report.
Hypermethylation was also detected in 28 of 30 peritoneal fluid samples from women with disease ranging from stages 1C to IV, including 3 with negative or atypical cytology.
In contrast, no hypermethylation was observed in tissues, fluid, or blood samples from the 40 women without cancer.
“Promoter hypermethylation is a common and relatively early event in ovarian tumorigenesis that can be detected in the serum DNA from patients with ovary-confined (stage 1A or B) tumors and in cytologically negative peritoneal fluid,” the investigators conclude.
Source: Cancer Res 2004;64:6476-6481. [ Google search on this article ]
MeSH Headings:Alkylation: Biological Sciences: Biology: Chemistry: Chemistry, Organic: Genetics: Genetics, Biochemical: Methylation: Molecular Biology: Physical Sciences: Genes, ras: DNA Methylation: Genes, BRCA1: Biological Sciences: Physical SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
