Johns Hopkins scientists have developed a gene-based test to distinguish harmless from precancerous pancreatic cysts. The test may eventually help some patients avoid needless surgery to remove the harmless variety. A report on the development is published in the July 20 issue of Science Translational Medicine.
The investigators estimate that fluid-filled cysts are identified in more than a million patients each year, most of whom have undergone CT or MRI scans to evaluate non-specific symptoms, such as abdominal pain and swelling.
Bert Vogelstein, M.D., co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator, and his colleagues analyzed precancerous cysts from 19 patients and searched for mutations in 169 cancer-causing genes. They found mutations in the KRAS gene, well-known for its prevalence in pancreatic cancers, and the GNAS gene, which had not previously been associated with pancreatic cancer. In both KRAS and GNAS, the mutations occur at a single coding spot in the DNA, the equivalent of a typo in a word within an entire encyclopedia. KRAS and GNAS genes produce signaling proteins, relaying signals from the cell surface to areas within the cell.
The researchers then tested a total of 132 precancerous pancreatic cysts for mutations in KRAS and GNAS. GNAS mutations were found in more than half of the samples (87 of them), and KRAS mutations occurred in 107 samples. Nearly all (127) had mutations in GNAS, KRAS or both. The mutations occurred in large and small, high- and low-grade cysts, and in all major types of the most common precancerous pancreatic cysts. There were no major differences in age, gender or smoking history for people with GNAS or KRAS mutations in their cysts’ cells. Read more…