Researchers at the Johns Hopkins Kimmel Cancer Center have found that a single genetic mistake causes about two-thirds of papillary thyroid cancers. Their research, published in the April 16 issue of the Journal of the National Cancer Institute, may lead to new therapies that could counteract the mistake.
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," said David Sidransky, 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," Sidransky said. "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.
Hopkins researchers also screened for the BRAF mutation in other cancers and thyroid tumors. They found a small percentage in lung and head and neck cancers. Six out of nine (66 percent) thyroid cancer cell lines tested positive for the BRAF mutation. No mutations were found in biopsies from 20 benign thyroid conditions and other types of thyroid cancer such as follicular, medullary and Hhrthle cell. A research team at the Wellcome Trust Sanger Institute recently found the same mutation in the BRAF gene in approximately 80 percent of melanomas and some colon cancers.
Thyroid cancer affects 22,000 Americans each year and makes up about half of all head and neck cancers. The thyroid gland essentially impacts all cells of the body by regulating metabolism, chemical balance and hormone production.
This research was partially funded by the National Cancer Institute.
Participants of this research include Yoram Cohen, Mingzhao Xing, Elizabeth Mambo, Zhongmin Guo, Guogun Wu, Barry Trink and Paul Ladenson from Johns Hopkins; and Uziel Beller from the University of the Negev, Jerusalem, Israel.