Two teams studying somatic mutations discovered this pre-malignant state in the course of researching other diseases. While most research into cancer focuses on the genetic mutations present in advanced stages of the disease, these two projects looked at how genes mutate over long periods of time; these are acquired mutations, or somatic mutation.
Steven McCarroll, senior author of one of the papers looked at DNA samples from 12,000 patients diagnosed with Bipolar disorder and/or schizophrenia. McCarroll is an assistant professor of genetics at Harvard Medical School and director of genetics at the Broad's Stanley Center for Psychiatric Research. The samples were taken from adults who were not diagnosed with cancer and showed no symptoms of any type of cancer.
They found that somatic mutations were concentrated in a handful of genes all of which were cancer genes. Using electronic medical records to follow the patients' subsequent medical histories, this team was able to show that the patients studied were 13 times more likely to develop certain blood cancers. McCarroll's team conducted follow-up analyses on tumor samples from two patients who had progressed from this pre-malignant state to cancer. These genomic analyses revealed that the cancer had indeed developed from the same cells that had harbored the "initiating" mutations years earlier.
Benjamin Ebert, an associate member of the Broad Institute and associate professor at Harvard Medical School and Brigham and Women's Hospital, is the senior author of the other paper. Ebert's team had hypothesized that since blood cancers increase in frequency with age, that it was possible that the genes were mutating over the lifetime of the patient and that perhaps these mutations could be detected earlier. Using data originally collected for the study of Type 2 Diabetes, the team looked at 17,000 DNA samples and specifically studied all 160 genes known to be mutated in most blood malignancies. They found that somatic mutations in these genes did indeed increase the likelihood of developing cancer, and they saw a clear association between age and the frequency of these mutations. They also found that men were slightly more likely to have mutations than women, and Hispanics were slightly less likely to have mutations than other groups. Ebert's team also found a relationship between these somatic mutations and morbidity from other diseases such as diabetes, coronary disease and ischemic strokes, however more study is needed to firmly establish that link.
"The fact that both teams converged on strikingly similar findings, using very different approaches and looking at DNA from very different sets of patients, has given us great confidence in the results," said Giulio Genovese, a computational biologist at the Broad and first author of McCarroll's paper. "It has been gratifying to have this corroboration of each other's findings."
The findings will be presented on December 9, 2014 at the American Society of Hematology Annual Meeting in San Francisco.