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

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

Summer Freeman | Newswise Science News
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>