-
- Posted Thursday September 30, 2010
TGen-Mayo Clinic study discovers role of DNA methylation in multiple myeloma
Report finds development of multiple myeloma is tied to
'hypomethylation'
PHOENIX, Ariz. - Sept. 30, 2010 - DNA methylation - a modification
of DNA linked to gene regulation - is altered with increasing
severity in a blood cancer called multiple myeloma, according to a
study by Mayo Clinic and the Translational Genomics Research
Institute (TGen).
And at specific points of DNA, "global hypomethylation," in which
many genes lose the modification, may be associated with the
step-by-step development of myeloma, according to a scientific
paper published this month in the journal Cancer Research.
"This is the first study to show that hypomethylation occurs early
in the development of multiple myeloma and increases through
disease progression," said Dr. Bodour Salhia, a TGen cancer
researcher and the paper's lead author.
DNA methylation suppresses the expression of viral genes and other
harmful elements incorporated over time into an individual's
genome. In cancer, hypermethylation at certain genomic locations
can turn tumor suppressing genes off, while hypomethylation in some
instances may lead to the over-expression of oncogenes, or those
genes that give rise to cancer, and is linked to chromosomal
instability.
However, there is still much to learn about the consequences of
altered methylation.
In this study, researchers examined the methylation status of more
than 1,500 CpGs. This is shorthand for C-phosphate-G, or cytosine
and guanine - two of the four chemicals that comprise DNA -
separated by a phosphate group, which links the two nucleosides
together.
Researchers used a high-throughput universal bead array technology
to examine CpG methylation at different stages of multiple myeloma,
evaluating DNA methylation events associated with the progression
of tumors.
They performed DNA methylation profiling analysis for more than 800
genes, including tumor suppressors, oncogenes, and genes involved
in cancer-related cellular processes. This process contrasts with
previous studies that focused on the analysis of a single
gene.
They found only a few genes that were hypermethylated, but
importantly found many more hypomethylated genes, even in the
earliest stages of multiple myeloma.
"Our data suggest that the overall degree of methylation may have
some prognostic value, and further studies are needed to determine
the functional and clinical significance of our findings," said Dr.
John Carpten, Director of TGen's Integrated Cancer Genomics
Division and the paper's senior author.
Dr. Salhia, added, "This study represents the most comprehensive
examination to date of the role of methylation in multiple myeloma,
and is expected to lead to an improved understanding of the
biological mechanisms involved in the development of this type of
cancer."
The study of DNA methylation falls under epigenetics - an emerging
field in cancer research. Unlike the study of genetics, epigenetics
refers to the study of gene activity that does not involve
hardwiring alterations in the genetic code. These epigenetic
events, which lay atop the genome, are an intricate and heritable
mechanism of regulating the expression of genes.
"Understanding the full spectrum of epigenetic modifications will
be key to improving the clinical management of the disease, and
studies should continue to find new ways of treating multiple
myeloma by targeting the multiple myeloma epigenome. This study
also emphasizes that hypomethylating strategies may not be the next
necessary steps in drug development." said Rafael Fonseca, M.D.,
Deputy Director of Mayo Clinic Cancer Center in Arizona.
Tissue samples and research collaboration was provided by the Mayo
Clinic in Arizona and the Multiple Myeloma Genomics Initiative, and
the Multiple Myeloma Research Consortium.
The Multiple Myeloma Research Foundation and the Multiple Myeloma
Research Consortium provided funding for the study.
Cancer Research is one of six peer-reviewed scientific journals
published by the Philadelphia-based American Association for Cancer
Research, founded in 1907, the world's oldest and largest
scientific organization focused on high-quality, innovative cancer
research.
*
About Mayo Clinic
Mayo Clinic is the first and largest integrated, not-for-profit
group practice in the world. Doctors from every medical specialty
work together to care for patients, joined by common systems and a
philosophy of "the needs of the patient come first." More than
3,700 physicians, scientists and researchers, and 50,100 allied
health staff work at Mayo Clinic, which has campuses in Rochester,
Minn.; Jacksonville, Fla.; and Scottsdale/Phoenix, Ariz.; and
community-based providers in more than 70 locations in southern
Minnesota, western Wisconsin and northeast Iowa. These locations
treat more than half a million people each year. Mayo Clinic Cancer
Center is one of 40 U.S. medical centers that have been named as a
National Cancer Institute (NCI) Comprehensive Cancer Center and the
only national, multi-site center with the designation. To obtain
the latest news releases from Mayo Clinic, go to
www.mayoclinic.org/news. For information about research and
education, visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com)
is available as a resource for your health stories.
Press Contact:
Jim McVeigh
Mayo Clinic Public Affairs
480-301-4222
[email protected]
*
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
# # #