S U M M E R U O F L M A G A Z I N E | 2 3
H A P P E N I N G H E R E
UofL team fi rst
to report gene
mutation role in
most glioblastomas,
melanomas
Researchers at the James Graham Brown Cancer Center have identif ed for the
f rst time mutations that destabilize a DNA structure that turns a gene off. These
mutations occur at four specif c sites in what is known as the "hTERT promoter"
in more than 75 percent of glioblastomas, a type of brain cancer, and melano-
mas, which are cancers of the skin.
The research was conducted by Brad Chaires, PhD; John Trent, PhD; Robert
Gray; William Dean, PhD; Robert Buscaglia; Shelia Thomas; and Donald Miller,
MD, PhD. The research was published in the online journal PLOS ONE.
The UofL team has shown that the mutations all occur in a region of what is
known as the human telomerase reverse transcriptase (hTERT) gene. This region
previously has been shown to form quadruplex DNA.
"We found that the mutations inactivate the gene's 'off ' switch so it becomes
locked on, destabilizing the quadruplex and allowing it to be over-expressed,"
Miller said. "This over-expression then drives the cells to continue to divide,
which is the cause of the cancer."
Miller