Navigation Links
CHOP experts collaborate in gene survey of childhood brain cancer; intriguing clues found

Pediatric cancer researchers at The Children's Hospital of Philadelphia contributed important expertise to a new landmark study of medulloblastoma, a type of brain tumor typically found in children. The large multicenter study defines the genetic landscape of this cancer, and holds intriguing clues to gene changes on signaling pathways that may become fruitful targets for future therapies.

The most common cancerous brain tumor in children, medulloblastoma is, fortunately, rare. However, it causes significant mortality, and survivors may suffer serious long-term side effects from treatment, so less toxic, more effective therapies are sorely needed.

The study appears online today in the journal Science. Collaborators from three countries and more than a dozen institutions co-authored the research, which was led by three scientists from Johns Hopkins University and the Howard Hughes Medical Institute: Bert Vogelstein, M.D., Kenneth Kinzler, Ph.D., and Victor Velculescu, M.D., Ph.D.

The researchers used recent innovations in gene-sequencing and informatics technology to analyze the whole exome (all the genes known to code for proteins) of medulloblastoma tumors. "This is the first application of whole-exome DNA sequencing analysis to a solid pediatric tumor, and there were encouraging results," said co-author Tom Curran, Ph.D., whose laboratory at The Children's Hospital of Philadelphia focuses on finding new treatments for medulloblastoma.

Curran added, "The study team found that the number of mutations in pediatric medulloblastoma tumors is five to ten times fewer than in adult medulloblastoma tumors. This suggests that, compared to adult tumors, pediatric tumors may respond better to drugs that target the genes and pathways altered by mutations that drive cancer progression. This is a hopeful finding."

In addition to detecting gene alterations previously found in medulloblastoma, such as mutations in the Hedgehog and Wnt signaling pathways, the current study also identified new and unexpected mutations in the MLL2 and MLL3 genes, genes not previously implicated in medulloblastoma. Both are tumor suppressor genes, genes that normally act as a brake on the development of cancer. If a mutation perturbs such a gene, cancer may then develop.

"Like other genes found in medulloblastoma, the MLL2 and MLL3 genes disrupt normal brain development during childhood," said co-author Peter C. Phillips, M.D., director of the Pediatric Neuro-oncology Program at The Children's Hospital of Philadelphia. "These genes interfere with biological signals during development, specifically with a process called histone methylation." In histone methylation, chemical tags that bind to DNA regulate how specific genes become active.

Both Curran and Phillips stressed the importance of collaboration among many institutions to the success of this study. "Even the largest oncology programs may see small numbers of medulloblastoma patients, so sharing data and materials is crucial to producing stronger statistical results," said Phillips. Children's Hospital and other centers have contributed resources and data to the Children's Brain Tumor Tissue Consortium, which provided tumor samples to the current study.

Direct clinical applications from this study are not immediate, but both researchers noted that clinical trials are already in progress to test whether inhibiting the Hedgehog pathway benefits medulloblastoma patients. Phillips added that the current study may lay a foundation for developing drugs that target the gene pathways associated with the MLL2 and MLL3 genes.


Contact: John Ascenzi
Children's Hospital of Philadelphia

Related medicine news :

1. Docs Claim Transplant Cured Man of HIV, But Experts Urge Caution
2. Youth Sports Injuries Reaching Epidemic Levels, Experts Report
3. Put Ladder Safety on Your Holiday To-Do List, Experts Say
4. Gun-Safety Talk a Safe Bet for All Families, Experts Say
5. Experts question whether patients will use performance data to choose their care
6. Experts urge US to create emergency cholera vaccine stockpile for humanitarian use
7. Cholera and vaccine experts urge United States to stockpile vaccine
8. Holiday Drinking Can Kill, Experts Warn
9. Airport Body Scanners Safe, Experts Say
10. Military experts provide civilian surgeons with guidance on handling bomb blast injuries
11. Winter Skies Still Pose Sun Danger, Experts Warn
Post Your Comments:
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg Traurig, P.A. ... The attorneys chosen by their peers for this recognition are considered among the top ... Shareholders received special honors as members of this year’s Legal Elite Hall of Fame: ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, CA is excited ... To Recovery® program to drive cancer patients to and from their cancer treatments. ... highest quality of life and ongoing independence. Getting to and from medical treatments ...
(Date:6/24/2016)... ... June 24, 2016 , ... People across the U.S. are sharpening ... Talker Award, an essay contest in which patients and their families pay tribute to ... at the 2016 National Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) this ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute ... Dr. Barry M. Weintraub as a prominent plastic surgeon and the network’s newest ... world, and the most handsome men, look naturally attractive. Plastic surgery should be ...
(Date:6/24/2016)... ... 2016 , ... Strategic Capital Partners, LLC (SCP) in concert ... capital for emerging technology companies. SCP has delivered investment events and professional ... than a million dollars of capital investment for five companies. The ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that it ... (procalcitonin) assay as a dedicated testing solution for people ... Roche is the first IVD company in the U.S ... assessment and management. PCT is a sepsis-specific ... blood can aid clinicians in assessing the risk of ...
(Date:6/23/2016)... June 23, 2016 , , ... July 7, 2016 , , , , LOCATION: , , ... , , , EXPERT PANELISTS:  , , , Frost & ... Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar and Unmesh Lal, ... The global pharmaceutical industry is witnessing an exceptional era. Several new ...
(Date:6/23/2016)... , June 23, 2016 The vast ... an outpatient dialysis facility.  Treatments are usually 3 times ... hours per visit, including travel time, equipment preparation and ... patient, but especially grueling for patients who are elderly ... a skilled nursing and rehabilitation centers for some duration ...
Breaking Medicine Technology: