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The Genetics of Pancreatic Cancer

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LKB1/STK11 - The Peutz-Jeghers Gene

This refers to a syndrome that runs in families, right?  Yes, early in this century a physician named Dr. Peutz described patients who had multiple polyps of their intestinal tract.   Later, Dr. Jeghers reported additional cases, some of them studied here at Johns Hopkins.  In the late 1980s, Dr. Giardiello of Hopkins reported that persons with this syndrome were at a high risk of developing pancreatic cancer.  In 1999, the Kern Laboratory, Dr. Hruban, and collaborators in The Netherlands worked together to find the proof of this association.  The patients with this syndrome were known to have one mutant copy of the LKB1/STK11 gene.  The Hopkins group found that in one of these patients' cancers, the remaining normal copy of the gene was lost.  They then also showed that about 5% of pancreatic and biliary cancers from patients without this syndrome, also had mutations or deletions of this gene.  This gene is therefore acting to prevent the emergence of pancreatic cancer, and genetic alterations of the gene occur in thousands of pancreatic cancers each year.