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Gene test predicts cancer potential in pancreatic cysts

20 July 2011

US researchers have developed a gene-based test to distinguish between pancreatic cysts that are harmless and those that are precancerous.

US researchers have developed a gene-based test to distinguish between pancreatic cysts that are harmless and those that are precancerous.

The test may eventually help some patients avoid needless surgery to remove the harmless variety.

The research team, from several Johns Hopkins medical institutions, estimates that more than a million people in the US alone develop pancreatic cysts but only a small number of these cysts will become cancerous. Most cysts are discovered when CT or MRI scans are used to investigate non-specific symptoms such as abdominal pain and swelling.

"Most cysts are benign," says pathologist Ralph Hruban, M.D., director of the Sol Goldman Pancreatic Cancer Research Center, "but distinguishing between the harmless and dangerous ones is challenging for doctors and patients alike."

Those that are not considered harmless are usually surgically removed, but the procedure requires removing part of the pancreas too, and complications can develop.

“There has long been a need for accurate, quantitative ways to identify cysts that are more worrisome and to help patients avoid unnecessary surgeries for harmless cysts,” said Bert Vogelstein, the Clayton Professor of Oncology at the Kimmel Cancer Center.

The team analysed precancerous cysts taken from a small number of patients and searched for mutations in a wide range of known cancer-causing genes. They found a similar mutation both in a specific gene known as KRAS, already well-known for its prevalence in pancreatic cancer, and also in the GNAS gene, which had not previously been associated with pancreatic cancer. In both cases, the mutation occurred at a single place in the DNA – the equivalent of a single misspelled word within an entire encyclopaedia.

Both genes produce signalling proteins which relaying signals from the cell surface to areas within the cell.

The researchers then examined a much larger sample of pancreatic cysts for mutations in these two genes. Nearly all (127 out of 132 cysts tested) had mutations in one or both of the genes.  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. Moreover, the mutations were not found in the non-cancerous cysts.

The researchers say that further studies on a larger number of patients must be carried out before the gene-based test can be widely offered. However, Bert Vogelstein, M.D., co-director of the Ludwig Center, says that the technology for developing a gene-based test in this case is relatively straightforward because the mutation occurs at one spot in both of the genes.

A report on the research is published in the July issue of Science Translational Medicine.

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