Hopkins researchers found a mutation of the BRAF (pronounced b-raf) gene in 68 percent (24 of 35 samples) of papillary thyroid cancers. These tumors account for about 75 percent of all thyroid cancer and occur mostly in women. "Until now, there have been no other major genetic events identified for common thyroid cancers," says David Sidransky, M.D., professor of otolaryngology and oncology at Johns Hopkins. "Our goal is to find better diagnostics and drug therapies designed to target the effects of this mutation."

The mistake involves a subtle change in the chemical bases (adenine, thymine, cytosine, and guanine) that make up DNA. The order in which these bases-or nucleotides-occur determines the information genes communicate to cells much like specific letters of the alphabet combine to form words and sentences. In the case of BRAF, the nucleotides are altered, and T (thymine) is switched to an A (adenine). The researchers found that this single coding error among more than 2000 nucleotides in the gene causes it to be stuck in the "on" position making thyroid cells continuously grow and divide, ultimately into cancer.

"Though most thyroid cancers can be cured by surgery and radioactive iodine treatments, it remains difficult to distinguish benign thyroid disease from cancer," says Sidransky. "Improvements in diagnostic tests and treatments using what we know about the BRAF mutation could speed up diagnosis and help patients survive advanced disease." Clinical trials for patients with papillary thyroid cancer who have not responded to surgery and radioactive iodine therapy are being planned.

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Contact: Valerie Matthews Mehl
mehlva@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
15-Apr-2003