Navigation Links
Genetic mutations that cause common childhood brain tumors identified

STANFORD, Calif. Researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital have identified several gene mutations responsible for the most common childhood brain tumor, called medulloblastoma, adding evidence to the theory that the diagnosis is a group of genetically distinct cancers with different prognoses. These and accompanying findings are likely to lead to less-toxic, better-targeted treatment approaches over the next two years, the researchers said.

"We tend to treat all medulloblastomas as one disease without taking into account how heterogeneous the tumors are at the molecular level," said Yoon-Jae Cho, MD, an assistant professor of neurology and neurological sciences at Stanford, a pediatric neurologist at Packard Children's and the senior author of the new research. "This paper represents a finer-grained view of the genetic landscape of these tumors and provides us with some leads on how to develop new therapies."

The research, which will appear online in Nature July 22, is part of a large, ongoing effort to characterize genetic errors in medulloblastoma. Two companion studies on which Cho is a co-author will be published simultaneously with his paper. The three papers came from a consortium that involves scientists at Stanford, Packard Children's, the Broad Institute, Children's Hospital Boston, the Dana-Farber Cancer Institute, the German Cancer Research Center, Brandeis University and the Hospital for Sick Children in Toronto.

Current treatment for medulloblastoma, which originates in the cerebellum and affects about 250 U.S. children each year, begins with surgery to remove as much of the tumor as possible. Patients then receive a combination of radiation and chemotherapy, but the treatments are not tailored to the tumor's genetic characteristics.

Cho's team extracted DNA from 92 medulloblastoma tumors and compared it with DNA from matched blood samples from the same patients, uncovering 12 significant "point mutations" single-letter errors in the genetic code that occurred frequently in the brain cancer. A handful of the mutations had been previously identified in smaller studies of medulloblastoma, but several mutations were novel in both medulloblastoma and in cancer.

Among the newly identified mutations was one in an RNA helicase gene, DDX3X, which Cho said is the second-most common mutation in medulloblastoma tumors. "Mutations in this gene have now also been identified in other tumor types, such as chronic lymphocytic leukemia, and head and neck tumors," he said.

However, the researchers found that it was rare for the same gene mutated in several different patients' tumors. More commonly, mutations involving a set of genes regulating a single biological pathway were found in the tumors a pattern that is emerging across cancer genome sequencing efforts.

Though no single tumor in the study carried all 12 mutations, the researchers were able to categorize the tumors according to which mutations they possessed. "We now understand that there are certain tumors with particular genetic signatures that are really resistant to standard treatments," Cho said. Children with medulloblastoma do not routinely have their tumors' genetic signatures characterized, but Cho believes that such characterization coupled with targeted therapies could greatly enhance tumor treatment.

About two-thirds of medulloblastoma patients now survive five years past diagnosis, but many survivors suffer lasting physical or intellectual side effects from their cancer treatments. Drugs tailored to a tumor's genetic profile have the potential to save more patients while reducing side effects, Cho said.

Several of the mutations discovered affect cellular signals that switch large groups of genes on and off. "The dysregulation of these 'epigenetic programs' is becoming a common theme not only in medulloblastoma but across cancer," Cho said. Such pathways may be good targets for cancer drugs; indeed, drugs targeting one such pathway (histone methyltransferases) are currently in pre-clinical development, while agents against another pathway (Hedgehog signaling pathway) are entering phase-2 clinical trials for medulloblastoma.

Cho is the co-chair of a committee within the Pediatric Brain Tumor Consortium that guides which drugs should be moved into clinical trials next. "Our plan is that within the next one to two years we will be able to offer kids a new set of compounds that have a clear biological rationale based on our genomic studies." Cho said. "We want to make sure we're being careful of what we move forward with, but at the same time, for some of these kids we don't have many, if any, effective and durable treatment options."


Contact: Erin Digitale
Stanford University Medical Center

Related medicine news :

1. Genetic markers for testosterone and estrogen level regulation identified
2. BUSM researchers identify genetic markers for testosterone, estrogen level regulation
3. Scientists discover melanoma-driving genetic changes caused by sun damage
4. Decline of immune system with aging may have a genetic cause
5. U-M researchers identify new genetic cause for chronic kidney disease
6. Turning off key piece of genetic coding eliminates toxic effect of statins, SLU research finds
7. Moffitt Cancer Center study validates activity of rare genetic variant in glioma
8. Trust hormone oxytocin found at heart of rare genetic disorder
9. Stanford study shows opiates side effects rooted in patients genetics
10. Holy glycosylation! New bat signal flags distressed cells in childhood genetic diseases
11. Study sheds new light on role of genetic mutations in colon cancer development
Post Your Comments:
(Date:6/27/2016)... ... June 27, 2016 , ... "FCPX editors can now reveal their ... Cut Pro X," said Christina Austin - CEO of Pixel Film Studios. , ... Pro X users can now reveal the media of their split screens with ...
(Date:6/26/2016)... ... , ... Quality metrics are proliferating in cancer care, and are derived from ... of the beholder, according to experts who offered insights and commentary in the current ... For the full issue, click here . , For the American Society of ...
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room ... Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. ... of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... A recent ... that most people are unfamiliar with. The article goes on to state that individuals ... also many of these less common operations such as calf and cheek reduction. The ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... LOS ANGELES , June 23, 2016 /PRNewswire/ ... (NASDAQ: CAPR ), a biotechnology company ... first-in-class therapeutics, today announced that patient enrollment in ... progrEssion in Duchenne) has exceeded 50% of its ... its enrollment in the third quarter of 2016, ...
(Date:6/23/2016)... Calif. , June 23, 2016 ... CST on Thursday, July 7, 2016 , , , , ... ) , , , , EXPERT PANELISTS:  , , ... Naik; Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar ... The global pharmaceutical industry is witnessing an exceptional ...
(Date:6/23/2016)... 23, 2016 Revolutionary technology includes ... Oticon , industry leaders in advanced audiology and hearing ... Oticon Opn ™, the world,s first internet connected hearing ... IoT devices.      (Photo: ... number of ,world firsts,: , TwinLink™ - ...
Breaking Medicine Technology: