Featured Research

from universities, journals, and other organizations

New genomics-based approach to understand origin of cancer subgroups

Date:
July 21, 2010
Source:
St. Jude Children's Research Hospital
Summary:
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. Now researchers have developed a new approach that uses genomic information from different species to understand the biology that drives the formation of these different cancer subtypes.

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. Now St. Jude researchers have 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 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.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Robert A. Johnson, Karen D. Wright, Helen Poppleton, Kumarasamypet M. Mohankumar, David Finkelstein, Stanley B. Pounds, Vikki Rand, Sarah E. S. Leary, Elsie White, Christopher Eden, Twala Hogg, Paul Northcott, Stephen Mack, Geoffrey Neale, Yong-Dong Wang, Beth Coyle, Jennifer Atkinson, Mariko DeWire, Tanya A. Kranenburg, Yancey Gillespie, Jeffrey C. Allen, Thomas Merchant, Fredrick A. Boop, Robert. A. Sanford, Amar Gajjar, David W. Ellison, Michael D. Taylor, Richard G. Grundy & Richard J. Gilbertson. Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature, 2010; DOI: 10.1038/nature09173

Cite This Page:

St. Jude Children's Research Hospital. "New genomics-based approach to understand origin of cancer subgroups." ScienceDaily. ScienceDaily, 21 July 2010. <www.sciencedaily.com/releases/2010/07/100718204809.htm>.
St. Jude Children's Research Hospital. (2010, July 21). New genomics-based approach to understand origin of cancer subgroups. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2010/07/100718204809.htm
St. Jude Children's Research Hospital. "New genomics-based approach to understand origin of cancer subgroups." ScienceDaily. www.sciencedaily.com/releases/2010/07/100718204809.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins