Early detection is important for patients with ovarian cancer, who, because of the late onset of clinical symptoms, are usually diagnosed with relatively advanced-stage disease. In an attempt to identify early disease markers, Ibanez de Caceres et al. have evaluated the methylation patterns of several tumour-suppressor genes.

Many genes have been shown to be hypermethylated in tumour cells and have been successfully used to identify patients with lung, head and neck, breast and bladder cancer — not directly from biopsy tissue, but in cells isolated from body fluids. This is feasible because methylated genes can be detected by a sensitive (1 methylated allele in 1,000 unmethylated alleles) methylation-specific PCR assay.

Ibanez de Caceres et al. used this method to determine the methylation status of two tumour-suppressor genes, BRCA1 and RASSF1A , in DNA isolated from tumour tissue and matched serum and peritoneal fluid from 50 ovarian or primary peritoneal tumours. Sixty-eight percent of the DNA samples isolated directly from the tumour tissue showed hypermethylation of one or both genes. The authors also analysed other tumour-suppressor genes — APC , CDKN2A (encoding INK4A and ARF) and DAPK — and increased detection of hypermethylated alleles to all 50 samples. A similar analysis of 21 archived stage I tumours revealed that 95% of samples had detectable levels of methylation at one or more of the six genes, confirming that hypermethylation is a marker of early-stage disease. Eighty-two percent of the matched serum and 93% of peritoneal fluid DNA showed an identical methylation pattern to that seen for the tumour DNA, indicating that body fluids, rather than tumour biopsy samples, could be analysed by this approach. Importantly, hypermethylation was not detected in tissue, serum or peritoneal-fluid DNA from 10 patients with benign ovarian disease or in serum DNA from 20 age-matched controls.

The authors concluded that analysis of the methylation pattern of these genes using serum DNA can identify individuals with ovarian cancer with 100% specificity and 82% selectivity. Improvements to the sensitivity of this approach might allow analysis of DNA hypermethylation to be developed as a non-invasive technique for identifying individuals with early-stage ovarian tumours.