Navigation Links
Childhood brain tumor traced to normal stem cells gone bad

BOSTON--An aggressive childhood brain tumor known as medulloblastoma originates in normal brain "stem" cells that turn malignant when acted on by a known mutant, cancer-causing oncogene, say researchers from Dana-Farber Cancer Institute and the University of California, San Francisco (UCSF).

Reporting in the Aug. 12 issue of Cancer Cell, the scientists say they have uncovered new origins for these tumors from early stem cells as well as more mature cells. Previously, scientists had assumed the tumors might only come from a single source: more mature cells which become neurons and do not have "stem" cell properties. The findings hint at potential new treatment approaches for medulloblastoma by targeting the origins of the tumors, and further suggest that not all patients' tumors may be born from the same cells.

"We now have a better idea of where these brain tumors come from and their relationship to normal stem cells in the brain," said Keith Ligon, MD, PhD, co-senior author of the report and an investigator at the Center for Molecular Oncologic Pathology at Dana-Farber and the Brigham and Women's Hospital in Boston.

Co-senior author, David Rowitch, MD, PhD, currently a professor of pediatrics and neurosurgery at UCSF and a Howard Hughes Medical Institute investigator, commented that mouse experiments shed light on how normal stem cells -- cells with the power to create all types of cells in the brain -- can be transformed into tumors. The transformation occurs when a cell-signaling pathway known as Sonic hedgehog (named for a cartoon character) is reactivated by a chance mutation.

Sonic hedgehog plays an important role during the embryonic development of the brain, but normally shuts down when it's no longer needed. When turned on again by a mutation, the signals can trigger cell processes leading to tumors -- not just in the brain, but in other organs as well.

Medulloblastomas, usually diagnosed in children between 2 and 5 years of age, affect the brain's cerebellum region, which is involved in controlling body movements. They make up about 30 percent of childhood brain tumors, and account for 250 to 300 new cases per year.

With current treatments, approximately 60 to 70 percent of patients live at least five years, but often they are left with cognitive disabilities from surgery, chemotherapy and radiation, urgently suggesting a need for new, more-selective therapies.

"Medulloblastoma was one of the first tumors that was believed to fit the hypothesis that tumors are caused by 'cancer stem cells' that initiate malignancies and sustain them," said Ligon, who is also on faculty and an assistant professor at Harvard Medical School. "But the prevailing hypothesis -- that medulloblastomas originate from non-stem cells just did not make perfect sense with this."

The discoveries emerged from a series of experiments begun in the Rowitch Laboratory at Dana-Farber. The initial goal was to determine whether activating the Sonic hedgehog cancer pathway in multiple types of brain cells, including neural stem cells, could help pinpoint which cells brain cancers might come from. Surprisingly, the scientists generated just one tumor type, medulloblastoma, regardless of whether they activated the pathway in stem cells for other cell types called neurons and glia. This was a surprise: it had been thought that medulloblastoma arose purely from neuronal ("thinking") cells and not "glial" or supporting cells.

An intriguing question for the investigators is why these cells, known as granule neuron precursors, seem to be uniquely vulnerable to the tumor-triggering effects of the Sonic hedgehog pathway, while other brain stem and progenitor cells are not.

Explained Rowitch: "There must be susceptibility factors in the granule neuron precursor cell that predispose it to forming cancer, so we now must try to understand what it is about this cell type that makes it susceptible to forming cancer in response to Sonic hedgehog signaling. This relationship between stem cells and oncogenes suggests a new point of potential therapeutic intervention."


Contact: Bill Schaller
Dana-Farber Cancer Institute

Related medicine news :

1. One-Fifth of British Childhood Cancer Survivors Smoke
2. String probes for devastating childhood digestive disease
3. 1/5 of British adult survivors of childhood cancer smoke despite hazards
4. YMCA Calls on Senate to Fund Community-Based Solutions to Address Childhood Obesity Crisis
5. St. Jude Study Reveals a New Function for an Old Enzyme in Fatal Childhood Disease
6. From Jet Engines to Search Engines, ORBIS-FedEx-Indiana University Join Forces to Fight Unnecessary Childhood Blindness
7. Aggressive treatment of childhood eczema could help prevent asthma, says new study
8. Topical oral syrup prevents early childhood caries
9. Stress during childhood increases the risk of allergies
10. U of M sets course for cure of fatal childhood skin disease
11. New Program/Website Targets Jewish Children, Teens, and Adults Suffering from the Impact of Childhood Maltreatment
Post Your Comments:
(Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand gesture animations, ... Christina Austin - CEO of Pixel Film Studios. , ProHand Cartoon’s package transforms ... Final Cut Pro X . Simply select a ProHand generator and drag it above ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... ... athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as ... City area —Johnson is one of the first doctors to perform the treatment. ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... A ... procedures that most people are unfamiliar with. The article goes on to state that ... but also many of these less common operations such as calf and cheek reduction. ...
(Date:6/24/2016)... PASADENA, CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. ... he would lash out at his family verbally and physically. , “When something upset him, ... table, he would use it. He would throw rocks at my other children and say ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. Amanda ... orthodontic treatment. Dr. Cheng has extensive experience with all areas of orthodontics, including ... accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... 23, 2016 Bracket , a leading clinical ... generation clinical outcomes platform, Bracket eCOA (SM) 6.0, at ... 26 – 30, 2016 in Philadelphia , ... Outcome Assessment product of its kind to fully integrate with ... Bracket eCOA 6.0 is a flexible platform for electronic clinical ...
(Date:6/23/2016)... , June 23, 2016  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a new affiliate ... in Latin America . ... ... ... ...
(Date:6/23/2016)... Pa. , June 23, 2016 The ... in an outpatient dialysis facility.  Treatments are usually 3 ... 6 hours per visit, including travel time, equipment preparation ... a patient, but especially grueling for patients who are ... of a skilled nursing and rehabilitation centers for some ...
Breaking Medicine Technology: