Scientists have identified the gene responsible for a rare form of endocrine tumor. The discovery, reported in today's issue of Science,* should lead to a genetic test for multiple endocrine neoplasia-type 1, or MEN1, which strikes fewer than one person in 10,000 and results in multiple benign tumors in the pituitary, parathyroid, and pancreas glands.
Stephen Marx of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, and colleagues at two other National Institutes of Health (NIH) labs teamed up in 1994 to hunt for the gene, which 8 years earlier had been mapped to chromosome 11 but then eluded detection. The researchers drew blood and tissue samples from members of 65 families afflicted with MEN1. They used a technique called positional cloning to piece together fragments from chromosome 11 and identify DNA stretches peculiar to people with the disease. "We had to check about 33 genes that map to the chromosome region, any one of which could have been it," says Francis Collins, director of the NIH's National Human Genome Research Institute. After screening for mutations in each candidate gene, the group at last pinpointed their quarry: a gene coding for a protein they have dubbed menin.
Endocrine gland cells multiply uncontrollably in adults with the mutated version of MEN1, the modus operandi of which is proving to be a tough nut to crack. It's "not like anything we've seen before," says Marx, who adds that his group has no clue how the healthy form of menin suppresses tumor growth. "This gene might be the first inroad into a whole metabolic pathway of cell regulation that we haven't had any insights into before," he says.
But even in the absence of an understanding of what MEN1 does, its discovery should lead to a test for the disease, in which benign tumors trigger debilitating symptoms such as hyperparathyroidism--a deregulation of calcium metabolism that can result in kidney stones and bone loss. Says endocrinologist Lorraine Fitzpatrick of the Mayo Clinic in Rochester, Minnesota, "This is important in terms of identifying who's at risk and working on ways to turn the mutated gene off."