In diverse ecosystems, packed with wildly different species, evolution whizzes along. As different species accumulate mutations, some adapt particularly well to their environment and prosper. It happens in marine sediments, mountain forests - and, as a new study illustrates, in precancerous tumors, too.
In a study published online in Nature Genetics, Carlo Maley, Ph.D., a researcher at The Wistar Institute, and his colleagues report that precancerous tumors containing a population of highly diverse cells were more likely to evolve into cancer than those containing genetically similar cells. The finding suggests that, in at least some forms of cancer, the more genetically diverse a precancerous tumor is, the more likely that tumor is to progress to full-blown cancer. If so, genetic diversity might act as a biomarker for cancer risk among patients with precancerous tissues.
"Although researchers first defined cancer in evolutionary terms in the 1970s, few researchers have actually studied the disease this way," says Maley, lead author on the study and an assistant professor in the molecular and cellular oncogenesis program at Wistar. "We wanted to know: If we measured a precancerous tumor's genetic diversity at baseline, could we predict who would go on to get cancer?"
To find out, the scientists decided to analyze data on a precancerous condition called Barrett's esophagus, in which cells lining the lower esophagus change due to repeated exposure to stomach acid from reflux, a condition often referred to as heartburn. Doctors typically adopt a "wait and watch" approach to treating patients with Barrett's esophagus because the condition only rarely leads to cancer and is difficult to treat surgically.
In the study, Maley and colleagues analyzed precancerous tumor data from 268 patients, including multiple biopsies within each tumor. On average, these patients were followed for 4.4 years, during which time 37 developed cancerous tumors. Overall, the database used in the study represents more than 32,000 distinct genotypes of different cells within the tumors.
Using computational techniques to analyze the data, the researchers calculated measures of diversity inside the tumors. Essentially, they counted cell varieties and measured the genetic difference, or divergence, between those varieties. "Simply put, we took ecology measures of species diversity and translated them into measures of cell diversity within tumors," Maley says. The found a striking correlation between increased diversity of tumor cells and progression to cancer. For every additional cell variety detected in a tumor, the patient was twice as likely to progress to cancer.