Nav: Home

DNA imprinting defects associated with childhood osteosarcoma development and progression

January 26, 2016

Children diagnosed with osteosarcoma may be impacted by a DNA imprinting defect also found in parents, according to new research from the Masonic Cancer Center, University of Minnesota. DNA imprinting is a phenomenon in which just one of the two inherited genes is active while the other is present but inactive.

The study is published now in the journal Oncotarget.

The research was spearheaded by Masonic Cancer Center researcher Subbaya Subramanian, Ph.D., associate professor in the University of Minnesota Medical School's Department of Surgery. The study was also collaboratively supported by David Largaespada, Ph.D., professor in the Department of Pediatric Hematology/Oncology and Clifford Steer, M.D., professor in the Departments of Medicine and Genetics, Cell Biology and Development. Both are members of the Masonic Cancer Center.

Osteosarcoma is a type of bone cancer predominantly affecting children and adolescents. The five year survival rate is about 70 percent, a rate unchanged in over 30 years. Recent research has shown a connection between downregulation of microRNAs and the development and progression of osteosarcoma. In this study, researchers wanted to know if the specific gene and microRNA expression changes associated with osteosarcoma could be due to epigenetic alterations and, specifically, if these alterations are also present in a parent.

Lead author Jingmin Shu, Ph.D., and the team assessed DNA methylation changes as well as reviewed histone modifications in both normal bone tissues and patient samples. Taking an even closer look, researchers also determined the imprinting status of a specific genomic location using the DNA from buccal swab samples from both osteosarcoma patients and their unaffected parents. Simultaneously, they observed pronounced imprinting defects in certain mouse models of osteosarcoma.

What they found

Results of the study show imprinting defects are associated with the pathogenesis of osteosarcoma and these imprinting defects are present in the DNA samples from affected children and their biological parents.

"Through these initial studies, we found the imprinting defects as possible mechanisms altering gene and microRNA expression which are associated with osteosarcoma pathobiology," said Subramanian. "This also allows us to think imprinting defects may be a cause for osteosarcoma to develop predominantly as a pediatric cancer."

They also cautiously noted that a larger cohort study is needed.

Other notable findings include:
  • Extent of gene expression and DNA methylation changes may identify the advancement of the disease.
  • The imprinting defect researchers found is unique to osteosarcoma.
  • Imprinting defects are not the result of pre-existing mutations in the mouse model.
"These findings set the stage for clinical investigation using DNA- and chromatin-modifying drugs, as well as rectifying imprinting defects by genome editing tools in osteosarcoma treatment," said Subramanian. "Further investigation is needed to evaluate novel methods to correct imprinting defects as preventive therapies."
This research was funded through grants from the American Cancer Society, the Karen Wyckoff Sarcoma Foundation, Children's Cancer Research Fund and Sobiech Osteosarcoma Fund.

University of Minnesota Academic Health Center

Related Dna Articles:

A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
More Dna News and Dna Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...