TGen-Mayo Clinic study discovers role of DNA methylation in multiple myeloma blood cancer

September 30, 2010

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.
-end-
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
mcveigh.jim@mayo.edu

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
syozwiak@tgen.org

The Translational Genomics Research Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.