Gene Test Predicts Cancer Potential in Pancreatic Cysts

Genetic analysis of precancerous fluid filled cysts and the search for mutations may eventually help more than a million patients each year avoid the possibility of needless surgery to remove the benign growths.

Scientists at Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA) analyzed DNA from the cyst fluid of 19 intraductal papillary mucinous neoplasms and the corresponding normal tissue by massively parallel sequencing for mutations in 169 cancer genes. Fourteen of the 19 tumors showed mutations in the known pancreatic oncogene Kirsten rat sarcoma viral oncogene homolog (KRAS), and 6 of the 19 carried a mutation in the stimulatory G-protein alpha subunit (GNAS), a well-known oncogene in other tumor types.

Of a larger set of fluid samples from these cystic neoplasms, 96% carried a mutation in at least one of the two oncogenes. In contrast, 44 benign cysts exhibited no GNAS or KRAS mutations. KRAS mutations did appear occasionally in a rare type of cyst with a relatively low potential to become cancerous. According to the investigators, these rare, mostly benign cysts are less challenging to diagnose because of their location within the pancreas and type of patient.

Generally, patients with a cyst that appears harmless and is less than 3 cm in size are monitored to watch for growth of the cyst or other concerning features such as a solid nodule. With cysts that appear more worrisome, surgical removal is often recommended, but the procedure requires removal of a portion of the pancreas as well, and complications like a pancreatic fistula where fluid from the pancreas leaks through the surgical incision, eating difficulties, and prolonged recovery can develop.

Bert Vogelstein, MD, a lead author of the study, said, "Further studies on a larger number of patients must be done before the gene-based test can be widely offered. However, 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." The study was published the July 20, 2011, issue of Science Translational Medicine.

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