A group of researchers
led by scientists from the Virginia Bioinformatics Institute at Virginia Tech
have developed a new technology that detects distinct genetic changes
differentiating cancer patients from healthy individuals. The advancement could
even serve as a future cancer predisposition test.
The multidisciplinary
team has created a design for a new DNA microarray that allows them to measure
the 2 million microsatellites (short, repetitive DNA sequences) found within
the human genome. Microsatellites, which tend to vary greatly among individuals
and have traditionally been used in forensics and paternity tests, are also
used to uncover information related to a number of other genetic diseases such
as Fragile-X or Huntington’s disease.
This advancement aided
the discovery of a unique pattern of microsatellite variation in breast cancer
patients that were not present in the DNA of patients who are cancer-free.
Through their evaluation of global changes in the genome, the researchers
determined that this pattern change alludes to a new mechanism disrupting the
genome in cancer patients and represents a new breast cancer risk biomarker.
There are indications that this could also serve as a general cancer signature.
The results of the work,
which includes contributions from researchers from the Univ. of Texas
Southwestern Medical Center, will be featured in Genes, Chromosomes and
Cancer.
“We have now arrived at a
new biomarker—an indicator that could be used to evaluate the amount of risk
that you have for developing cancer in the future,” explained Virginia
Bioinformatics Institute Executive Director Harold “Skip” Garner, who also
leads the institute’s Medical Informatics and Systems Division. “This is part of an
effort to understand their (microsatellite) role in the genome and then proceed
on directly towards something that is of utility in the clinic. What just came
out in our paper is a description of the technology that allows us to very
quickly and efficiently and inexpensively measure these 2 million places using
a uniquely designed microarray. It’s the pattern on that microarray that
provides us the information we need.”
Only a small percentage
of microsatellites have been linked to cancer and other diseases because there
hasn’t been an effective method available for evaluating large numbers of these
sequences. This technology is enabling scientists to understand the role of
these understudied parts of our genome for the first time and may help explain
the difference between the known genetic components in disease and those that
have been explained by genomic studies. This tool can be used to identify
and better understand genetic changes in many different types of cancer with
the potential to serve as a universal cancer biomarker. It has already been
instrumental in the discovery of a new biomarker in the estrogen-related receptor gamma
(ERR-?) gene, which indicates an individual’s increased risk for breast cancer.
The group is now pursuing a number of these cancer predisposition risk markers
in colon, lung, and other cancers.
This work was funded by
the Virginia Bioinformatics Institute at Virginia Tech, the P.O’B Montgomery
Distinguished Chair in Developmental Biology, and an National Institutes of
Health Cardiology Fellowship, and was partially supported by the University of
Texas’ National Institutes of Health’s National Cancer Institute SPORE project
(P50CA70907).
