Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Develop New Genomics-Based Approach to Understand the Origin of Cancer Subgroups

21.07.2010
Unique combinations of cells and mutations lie at the heart of cancer subgroup revealed for the first time in a pediatric brain tumor

Scientists have long recognized that cancers may look the same under the microscope, but carry different mutations, respond differently to treatment and result in vastly different outcomes for patients. An international team led by St. Jude Children’s Research Hospital scientists has developed a new approach that uses genomic information from different species to understand the biology that drives the formation of these different cancer subtypes.

The approach was developed by studying a tumor called ependymoma that affects the brains and spines of children and adults, but may also translate to other forms of cancer. The research demonstrates for the first time that ependymomas in different regions of the nervous system arise when subtypes of stem cells found there acquire specific mutations. The research also led to discovery of the first gene, called EPHB2, proven to cause ependymoma and has created the first accurate laboratory model of this disease. The research was published in the advance online publication of the prominent scientific journal Nature and is authored by Richard Gilbertson, M.D., Ph.D., a member of the St. Jude Departments of Developmental Neurobiology and Oncology.

“The approach we have developed provides a flexible way for scientists around the world to test the hypothesis that subsets of different cancers arise when particular mutations occur in particular cell types,” Gilbertson said. “Because the laboratory models developed from this approach accurately model patient subgroups, they can then be used to develop and tailor effective new treatments for these patients.”

The project builds on earlier work from Gilbertson’s laboratory into the role that normal stem cells play in cancer. The body relies on stem cells, which can divide and take on more specialized functions, to keep organs repaired and operating smoothly. The research included scientists from seven institutions in the U.S., Canada and Great Britain.

For this study, investigators gathered 204 ependymomas from patients in the U.S., Canada and Europe to conduct the most comprehensive analysis yet of the ependymoma genome. Researchers found the pattern of DNA gain or loss differed depending on the ependymoma’s location in the brain or spine and uncovered nine subtypes of the disease. The analysis also identified more than 200 genes as potentially important for triggering the tumor or helping the cancer spread. The list included EPHB2, a gene that regulates stem cell division and was recently linked to intestinal tumors. In this study, investigators linked EPHB2 to just one ependymoma subtype.

Researchers also tracked the different stem cell populations that give rise to ependymomas. Using an algorithm developed by Stanley Pounds, Ph.D., associate member in the St. Jude Department of Biostatistics, researchers compared patterns of gene expression in human ependymomas with gene expression in stem cells from different regions of the nervous systems of both embryonic and adult mice. The mathematical tool made it possible for the first time to compare global gene expression patterns between species.

The exercise linked one subtype of the human cancer with a particular subpopulation of mouse nervous system or neural stem cells. The stem cells also lacked the tumor suppressor genes Ink4a/Arf. When extra copies of EPHB2 were added to those neural stem cells and the cells were implanted in the forebrains of mice, half the mice developed brain tumors within 200 days. Scientists went on to show the tumors were identical to human ependymomas by several different measures. In contrast, no ependymomas developed when extra copies of EPHB2 were inserted into other subpopulations of mouse neural stem cells.

Additional testing found that the mouse ependymoma model matched just one subtype of human ependymomas but no other form of common human brain tumors.

The study’s other authors are Robert Johnson, Karen Wright, Helen Poppleton, Kumarasamypet Mohankumar, David Finkelstein, Elsie White, Christopher Eden, Twala Hogg, Geoffrey Neale, Yong-Dong Wang, Jennifer Atkinson, Mariko DeWire, Tanya Kranenburg, Thomas Merchant, Fredrick Boop, Robert Sanford, Amar Gajjar and David Ellison, all of St. Jude; Vikki Rand, University of Newcastle upon Tyne, U.K.; Sarah Leary, Seattle Children’s Hospital; Paul Northcott, Stephen Mack and Michael Taylor, all of the Hospital for Sick Children, Toronto; Beth Coyle and Richard Grundy, both of the University of Nottingham, U.K.; Yancey Gillespie, University of Alabama, Birmingham; and Jeffrey Allen, New York University Langone Medical Center, New York.

The work was supported in part by the National Institutes of Health, the Collaborative Ependymoma Research Network and ALSAC.

St. Jude Children's Research Hospital
St. Jude Children’s Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer and other catastrophic diseases. Ranked the No. 1 pediatric cancer hospital by Parents magazine and the No. 1 children’s cancer hospital by U.S. News & World Report, St. Jude is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. St. Jude has treated children from all 50 states and from around the world, serving as a trusted resource for physicians and researchers. St. Jude has developed research protocols that helped push overall survival rates for childhood cancer from less than 20 percent when the hospital opened to almost 80 percent today. St. Jude is the national coordinating center for the Pediatric Brain Tumor Consortium and the Childhood Cancer Survivor Study. In addition to pediatric cancer research, St. Jude is also a leader in sickle cell disease research and is a globally prominent research center for influenza.

Founded in 1962 by the late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world, publishing more research articles than any other pediatric cancer research center in the United States. St. Jude treats more than 5,700 patients each year and is the only pediatric cancer research center where families never pay for treatment not covered by insurance. St. Jude is financially supported by thousands of individual donors, organizations and corporations without which the hospital’s work would not be possible. In 2010, St. Jude was ranked the most trusted charity in the nation in a public survey conducted by Harris Interactive, a highly respected international polling and research firm. For more information, go to www.stjude.org.

Summer Freeman | Newswise Science News
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>