Method finds and quantifies hypermethylated RASSF1A in blood.

Researchers discovered a blood screening technique that could make it possible to detect early-stage hepatocellular carcinoma (HCC) and predict how well a patient will do following treatment.

Scientists previously knew that the DNA of HCC tumor cells lack a functioning copy of RASSF1A, due to hypermethylation. Methylation-specific PCR, however, destroys about 85–93% of the DNA in a blood sample. Together with the fact that tumoral DNA is only present at very low concentrations in blood during early stages of HCC, this method has not been sensitive enough to detect altered RASSF1A in blood, reports K.C. Allen Chan, a professor at the Chinese University of Hong Kong.

To compensate, Chan and his colleagues invented a new technique that they call methylation-sensitive enzyme-mediated real-time PCR. This combines real-time PCR with an enzyme that breaks unmethylated DNA apart. With this new method, Chan’s team was able to separate out the altered methylated DNA.

To test the relationship between altered RASSF1A and HCC, Chan’s team conducted two studies involving HCC patients. In the first, they matched 63 pairs of patients, one with HCC and the other a chronic HBV carrier by age and sex, with 30 healthy volunteers. They detected hypermethylated RASSF1A in 93% of the HCC patients, in 58% of the HBV carriers, and in none of the healthy patients. The median RASSF1A levels for the HCC patients were 770 copies per mL and 118 copies per mL for HBV carriers.

In the second study, the researchers looked at 22 pairs of sex- and age-matched patients who had been enrolled in a HCC surveillance program involving 1,018 HBV carriers. For the 22 HBV carriers who subsequently developed HCC, there was a significant increase in circulating RASSF1A levels from the time of enrollment to the time of cancer diagnosis. On the contrary, there was no significant change in RASSF1A levels over the same period for the 22 matched subjects enrolled in the same program who didn’t develop HCC.

The team is presenting their data on September 18 at the American Association for Cancer Research’s “Second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.”

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