Scientists at Johns Hopkins have provided more clues to one of the least understood phenomena in some cancers: why the "ends caps" of cellular DNA, called telomeres, lengthen instead of shorten.
In a study published online June 30 in Science Express, the Johns Hopkins researchers say they have identified two genes that, when defective, may cause these telomere elongations.
Telomeres contain repeated sequences of DNA that, in normal cells, shorten each time a cell divides. Without telomeres, the cell division-related shortening could snip off a cell's genes and disrupt key cell functions. Most cancer cells, naturally prone to divide rapidly, use high amounts of an enzyme called telomerase to keep their telomeres intact. Yet, some cancer cells are known to maintain their telomere length without help from telomerase.
With no increased production of telomerase, scientists were left to wonder how cancer cells managed to maintain their telomeres, a phenomenon known as "alternative lengthening of telomeres."
"Finding the genes responsible for alternative lengthening of telomeres is the first step in understanding this process and provides opportunities to develop new drug therapies," says Nickolas Papadopoulos, Ph.D., associate professor at the Johns Hopkins Kimmel Cancer Center and director of translational genetics at Johns Hopkins' Ludwig Center.
The first clues to the genes linked to the process came from a study led by Papadopoulos that mapped the genome of pancreatic neuroendocrine tumors, published in the Jan. 20 issue of Science Express. The most prevalent gene alterations in those tumors occurred in genes that include ATRX and DAXX. Proteins made by these genes interact with specific portions of DNA to alter how its chemical letters are read. ATRX and DAXX had also been linked to similar functions in the telomere region, says Alan Meeker, Ph.D., assistant professor of pathology, urology and oncology
|Contact: Vanessa Wasta|
Johns Hopkins Medical Institutions