Navigation Links
Key mutations discovered for most common childhood brain cancer
Date:7/22/2012

Boston, Mass., July 22, 2012 Researchers at Dana-Farber/Children's Hospital Cancer Center (DF/CHCC) and several collaborating institutions have linked mutations in specific genes to each of the four recognized subtypes of medulloblastoma, the most common malignant brain tumor of children. The discovery, reported July in the journal Nature, provides doctors with potential biomarkers for guiding and individualizing treatment and reveals prospective therapeutic opportunities for countering this devastating malignancy.

The study was conducted by a research team led by Scott Pomeroy, MD, PhD, Neurologist-in-Chief at Boston Children's Hospital and a neuro-oncologist at DF/CHCC; Yoon-Jae Cho, MD, formerly of Boston Children's and now at Stanford University School of Medicine; and Matthew Meyerson, MD, PhD, of Dana-Farber Cancer Institute and the Broad Institute.

Medulloblastomas occur in the cerebellum (the part of the brain that controls balance and other complex motor functions) and are treated with a combination of surgery, radiation and chemotherapy. Though overall survival hovers around 70 percent, most survivors are unable to live independently due to the lasting effects of both tumor and treatment.

Doctors have historically classified medulloblastoma patients as either standard or high risk based on biopsy results, but have long suspected that what we call medulloblastoma could actually be several different diseases. Over the last two years, studies by researchers including Pomeroy and his colleagues have bolstered this view by dividing medulloblastoma into four molecular subtypes based on gene expression profiles and copy number variations. Each subtype has a distinct survival rate, ranging from 20 to 90 percent.

"Not only do we now know how to stratify medulloblastomas genomically, we have a firm grasp of what gene mutations drive each molecular subtype," said Pomeroy, who has spent 20 years trying to understand the biological basis of the tumor's variability. "For the first time, we'll be able to classify and treat medulloblastoma based on molecular typing, providing the best therapy with the fewest long-term consequences."

In this new study, Pomeroy and his team used next generation sequencing technologies to read the full complement of protein-coding genes (also called the exome) of tumors from 92 patients. Within these tumors the team discovered that somatic (that is, non-heritable) mutations occur at very low frequency, one-tenth to one-hundredth of that seen in cancers of adults. Specific gene mutations clustered neatly into the four molecular subtypes, although the majority of genes (88%) were mutated only once in the entire tumor collection. Only 12 genes were mutated in more than one tumor, illustrating medulloblastoma's genetic heterogeneity.

Functionally, the mutated genes fell into two broad categories: genes like Shh and Wnt that play direct roles in molecular pathways controlling cell growth, and genes like DDX3X and GPS2 that play more of a coaching role, modulating the activity of other genes.

Taken as a whole, the study's results confirm the view of medulloblastoma as a family of tumors driven by disruptions in just a few common mechanisms. However, the form those disruptions takethe actual mutations or genomic changescan vary from tumor to tumor.

"The results reflect two emerging genetic themes seen throughout childhood tumors," Pomeroy noted. "First, very low mutation rates, much lower than those seen in adult tumors, and second, the importance of mutations in genes that regulate the function of the cell's growth pathways but which aren't direct components of those pathways."

Some of the study's findings could be translated to patients relatively quickly. For instance, with the main mutations of each subtype in hand, it should soon be possible to rapidly classify individual medulloblastoma patients' tumors and tailor treatment appropriately based on each subtype's known prognosis. In addition, clinical trials of Shh-blocking drugs already under investigation for other cancers could begin within the next couple of years in patients with the medulloblastoma subtype driven by Shh mutations.

Pomeroy credits the high level of cooperation between groups at different institutions studying medulloblastoma as a significant factor in the progress made over the last few years. "Because of our collective efforts, medulloblastoma has gone from an important but obscure tumor to one that we understand better than many other cancers at the molecular level."


'/>"/>

Contact: Meghan Weber
meghan.weber@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related biology news :

1. New gene mutations linked to ALS and nerve cell growth dysfunction
2. UMMS researchers isolate gene mutations in patients with inherited amyotrophic lateral sclerosis
3. Mutations in autism susceptibility gene increase risk in boys
4. Interacting mutations promote diversity
5. Gene mutations cause massive brain asymmetry
6. BRG1 mutations confer resistance to hormones in lung cancer
7. Virus discovered in Cultus Lake sport fish
8. Genetic link to rapid weight gain from antipsychotics discovered
9. Fossil egg discovered in Lleida (Spain) links dinosaurs to modern birds
10. Can you hear me now? New strategy discovered to prevent hearing loss
11. Feathered saurians -- downy dinosaur discovered
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/21/2016)... , March 22, 2016 ... with passcodes for superior security   ... leading provider of secure digital communications services, today announced ... technology and offer enterprise customers, particularly those in the ... recognition and voice authentication within a mobile app, alongside, ...
(Date:3/14/2016)... , March 14, 2016 NXTD ... growing mobile commerce market, announces the airing of a new ... starting the week of March 21 st .  The commercials ... including its popular Squawk on the Street show. --> ... on the growing mobile commerce market, announces the airing of ...
(Date:3/10/2016)... , March 10, 2016   Unisys Corporation ... and Border Protection (CBP) is testing its biometric identity ... San Diego to help identify certain non-U.S. citizens ... . The test, designed to help determine the efficiency and ... began in February and will run until May 2016. ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... ... May 25, 2016 , ... The ... by the Office of the National Coordinator for Health IT (ONC) outlining a ... clinically relevant data were available when and where it was needed. The organization ...
(Date:5/25/2016)... UTAH. (PRWEB) , ... May 25, 2016 , ... WEDI, ... healthcare information exchange, today announced that Charles W. Stellar has been named by the ... interim CEO since January 2016. As an executive leader with more than 35 years ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... Drug Administration (FDA) has granted the company’s orphan drug designation request covering BHV-4157 ... drug designation granted by the FDA. , Spinocerebellar ataxia is a rare, ...
(Date:5/24/2016)... 2016   MedyMatch Technology Ltd ., the data analytics ... decision support tools in the emergency room, announced today that ... Advanced Technology Industries (IATI) BioMed Conference. The ... 15th National Life Sciences and Technology Week, and is being ... in Tel Aviv, Israel . Gene ...
Breaking Biology Technology: