Discoveries
Investigation probes timing of gene mutations in cancer
Research into an extremely rare condition is helping Dana-Farber investigators fill in the picture of the earliest stirrings of cancer.
The transformation of a normal cell into a cancerous one results from a series of errors in which gene abnormalities, or mutations, accumulate until the normal controls on the cell's growth and division are crippled. Increasingly, scientists are realizing that the order in which mutations occur plays an important role in cancer cells' behavior and aggressiveness.
New evidence for that idea came in a study by researchers at Dana-Farber and affiliated Brigham and Women's Hospital. Led by Nabeel Bardeesy, PhD, and Ronald DePinho, MD, of DFCI's Medical Oncology Department, the investigators focused on a rare disorder known as Peutz-Jeghers syndrome (PJS), which triggers problems ranging from noncancerous growths in the intestines to malignant tumors of the pancreas, intestine, stomach, and breast.
A discovery by Finnish scientists that at least half of PJS patients have a mutation in a particular gene raised a question for researchers: How can a single genetic error be responsible for both benign and malignant growths? Using a special strain of mouse, Bardeesy, DePinho, and their colleagues found that mutations in the gene not only remove the normal brakes on cell growth, but also block other genes from propelling the cell toward cancer. "The mutations seem to make cells both more and less susceptible to becoming cancerous," says Bardeesy.
Researchers theorize the paradox involves the timing of the mutations. "When the mutations occur in normal cells, the cells may grow irregularly but become resistant to further cancer-causing changes," DePinho remarks. When the mutations happen in cells already on the road to cancer, however, they may push the cells further into an abnormal, fast-growing state. Other studies will seek to confirm whether that is, indeed, the case.
