Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Researchers Lead Largest-ever Sequencing Study of Neuroblastoma

Published: Wednesday, January 23, 2013
Last Updated: Wednesday, January 23, 2013
Bookmark and Share
An extensive genomic study of the childhood cancer neuroblastoma reinforces the challenges in treating the most aggressive forms of this disease.

Contrary to expectations, the scientists found relatively few recurrent gene mutations—mutations that would suggest new targets for neuroblastoma treatment. Instead, say the researchers, they have now refocused on how neuroblastoma tumors evolve in response to medicine and other factors.

“This research underscores the fact that tumor cells often change rapidly over time, so more effective treatments for this aggressive cancer will need to account for the dynamic nature of neuroblastoma,” said study leader John M. Maris, MD, director of the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia (CHOP).

Striking the peripheral nervous system, neuroblastoma usually appears as a solid tumor in a young child’s chest or abdomen. It comprises 7 percent of all childhood cancers, but causes 10 to 15 percent of all childhood cancer-related deaths. Neuroblastoma is notoriously complex, with a broad number of gene changes that can give rise to the disease.

Largest-ever genomic study of high-risk neuroblastoma patients

Maris headed the multicenter research collaborative, the TARGET (Therapeutically Applicable Research to Generate Effective Treatments) initiative, which released its findings today in Nature Genetics. This largest-ever genomic study of a childhood cancer analyzed DNA from 240 children with high-risk neuroblastomas. Using a combination of whole-exome, whole-genome and transcriptome sequencing, the study compared DNA from tumors with DNA in normal cells from the same patients.
Researchers at CHOP and other centers previously discovered neuroblastoma-causing mutations, such as those in the ALK gene. In the subset of patients carrying this mutation, oncologists can provide effective treatments tailored to their genetic profile.

“A few years ago, we thought we would be able to sequence the genomes of individual patients with neuroblastoma, detect their specific cancer-causing mutations, and then select from a menu of treatments,” said Maris. The oncology researchers designed the TARGET study to perform genomic analyses of a large cohort of high-risk neuroblastoma patients, with the goal of mapping out a limited number of treatment strategies. This approach would represent a significant step forward in personalizing neuroblastoma therapy.

Study findings

However, while the researchers confirmed that roughly 10 percent of the study’s neuroblastoma patients had ALK mutations, and found that a handful of other gene mutations each accounted for percentages in the single digits, there were relatively few recurrent mutations in somatic (non-germline) cells. “The relative paucity of recurrent mutations challenges the concept that druggable targets can be defined in each patient by DNA sequencing alone,” wrote the authors.

In the absence of frequently altered oncogenes that drive high-risk neuroblastomas, the authors concluded that most such cases may result from other changes: rare germline mutations, copy number variations and epigenetic modifications during tumor evolution.

“Personalized medicine is more complex than we had hoped,” said Maris. “While there are successes such as those in treating patients whose tumors harbor ALK mutations, this study implies that we must think very differently about how we’ll use genomics to define treatment.” Maris added that neuroblastoma researchers may need to turn to functional genomics, learning which tumors will or won’t respond to treatments, as well as going beyond a static picture of a cancer cell with fixed genetic contents, to devising interventions to deal with dynamic tumor cells that evolve during nervous system development.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Tuesday, August 25, 2015
Gene that Causes Childhood Cancer Neuroblastoma is Found
The researchers found that the same gene mutations play a significant role in high-risk forms of non-inherited neuroblastoma.
Tuesday, August 26, 2008
Pediatric Researchers Find Possible 'Master Switch' Gene in Juvenile Arthritis
A gene region known to play a role in some varieties of adult rheumatoid arthritis is also present in all types of childhood arthritis, researchers say.
Tuesday, July 08, 2008
Genetics Researcher Receives First CdLS Fellowship
CdLS Foundation has awarded its first ever fellowship to a researcher at The Children's Hospital of Philadelphia, to support research into the genetic causes of the disease.
Monday, July 07, 2008
Scientific News
Genes That Protect African Children From Developing Malaria Identified
Variations in DNA at a specific location on the genome that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the life-threatening disease, have been identified in the largest genetic association study of malaria to date.
Researchers Disguise Drugs As Platelets to Target Cancer
Researchers have for the first time developed a technique that coats anticancer drugs in membranes made from a patient’s own platelets.
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Scientists Create World’s Largest Catalog of Human Genomic Variation
An international team of scientists from the 1000 Genomes Project Consortium has created the world’s largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why some people are susceptible to various diseases.
Five Genetic Regions Implicated In Cystic Fibrosis Severity
An international consortium of researchers conducted the largest-ever CF genome-wide analysis to find new therapeutic targets.
Greater Understanding Of Polycystic Ovary Syndrome
A new genetic study of over 200,000 women reveals the underlying mechanisms of polycystic ovary syndrome, as well as potential interventions.
New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
A Fundamental Protection Mechanism Against Formalin In Mammals is Revealed
Formaldehyde, or formalin, is well known to all of us as a common chemical used in many industrial processes and also as a preservative, remarkably we also produce formaldehyde in our bodies.
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos