Normal tissues of cancer patients are not normal as evidenced by the high incidence of metachronous cancers. This has been long known as field cancerization, but demonstration of mechanism was elusive due to subtle nature of mutation accumulation in normal cells. In contrast, aberrant DNA methylation can be accumulated at high levels. In the stomach, aberrant DNA methylation is induced by Helicobacter pylori infection, and accumulation level of aberrant DNA methylation is correlated with cancer risk. Mechanistically, chronic inflammation induces aberrant DNA methylation by repressing Tet expression and increasing DNMT activity.

A direct application is patient stratification for cancer risk. Prediction of the risk of metachronous gastric cancer was achieved by a prospective study. Another prospective study in 1,800 healthy people after H. pylori eradication has now produced a promising result.

The methylation signature in cells can mark them. Specific signature in cells with intestinal metaplasia (IM) showed that IM cells have higher chance of conversion into cancer cells, showing the precancerous nature of IM.

HOST:
Prof Patrick Tan
Senior Vice Dean, Research
Duke-NUS Medical School

VENUE:
National Cancer Centre Singapore
NCCS Lecture Theatre, Level 1

CONTACT:
Ms Kathleen Chan
Duke-NUS Research Affairs Department
Email: kathleen.chan@duke-nus.edu.sg