Drug & Device Development

Hypermethylated DNA in circulation of patients with HBV predicts liver cancer

Last Updated: 2007-09-20 16:14:43 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - New methodology developed by scientists at the Chinese University of Hong Kong can detect and quantify serum levels of a hypermethylated tumor suppressor gene associated with hepatocellular carcinoma (HCC). Dr. K. C. Allen Chan presented their findings at the second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, held this week in Atlanta, Georgia.

HCC is of particular concern in China, Dr. Chan said in an interview with Reuters Health. "Nearly 10% of the population in China are HBV (hepatitis B virus) carriers, and their risk of developing HCC is increased 100-fold compared with that of the general population."

Population screening for HCC with ultrasound and CT scans is too expensive, Dr. Chan added, and current laboratory tests lack sensitivity.

To develop a screening blood test, the research team focused their efforts on hypermethylation of the tumor suppressor gene RASSF1A, which is characteristic of HCC, and developed a new technique that involves real-time PCR after methylation-sensitive restriction enzyme digestion.

Testing their new technique on blood samples from 63 patients with HCC, 63 subjects with chronic HBV, and 30 healthy volunteers, they were able to detect hypermethylated RASSF1A in 93%, 58% and 0% of subjects, respectively.

Median levels of the inactivated gene were 770 copies/mL in the cancer patients and 118 copies/mL among the HBV carriers (p < 0.0001).

The levels in HBV carriers suggest that "RASSF1A hypermethylation is an early event in HCC pathogenesis and can be found in premalignant liver tissues," according to their meeting abstract. Higher serum concentrations were associated with poor prognosis.

Furthermore, in a surveillance group of HBV carriers tracked between 1997 and 2007, inactivated RASSF1A levels were low at baseline. Increasing serum levels during follow-up were significantly associated with HCC diagnosis, Dr. Chan told Reuters Health, while stable low levels were found in subjects who did not develop HCC.

Dr. Chan believes that "methylation-sensitive enzyme-mediated real-time PCR" will be cost-effective for mass screening after further development.

Although the investigators had restricted their research to HBV carriers and HCC patients, "hypermethylated genes are also present in breast cancer and lung cancer," Dr. Chan pointed out, and future research using their new technology may also identify biomarkers for these diseases.