More and more mutations clutter up our DNA as we age. Mostly, these don’t cause problems. But sometimes, a switch will flip, and a mutated cell turns cancerous. Can we see this shift in time to prevent or treat cancer before it starts?
Led by researchers at Fred Hutchinson Cancer Research Center, a scientific team that studies a precancerous condition of the esophagus (called Barrett’s esophagus or BE) are working to answer this question. In work published today in Nature Communications, the team revealed that DNA changes in BE cells that presage esophageal cancer can be spotted years before cancer develops.
The characteristic changes include rearrangements of large chunks of DNA and damage to both copies of a tumor-suppressing gene called TP53.
“Most patients who progressed [to esophageal cancer] had two ‘hits’ [changes that likely inactivate normal gene function] to TP53,” said Dr. Thomas Paulson, a senior staff scientist in the Grady Lab who co-led the project. “In these patients, cells with altered TP53 had spread to larger regions of the esophagus and persisted over longer periods of time compared to patients who didn’t progress to cancer.”
Though the team’s ultimate goal is to improve diagnostics and screening for esophageal cancer, Paulson emphasized that this study compares the mutations and DNA changes that occurred in patients who progressed to cancer with those that occurred in patients with stable, benign BE. While the findings are significant and are based on analysis of over 400 tissue samples, results from this 80-patient study would need to be validated in other patient groups before they could be used clinically to predict whether other BE patients will progress to cancer, he said.
