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

NIH Scientists Map Genetic Changes that Drive Tumors in Rhabdomyosarcoma

Published: Monday, January 27, 2014
Last Updated: Sunday, January 26, 2014
Bookmark and Share
The genetic alterations identified could be useful in developing targeted diagnostic tools and treatments for children with the disease.

Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric soft-tissue cancer, and found that the disease is characterized by two distinct genotypes.

The study, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues, appeared in the Jan. 23, 2014, issue of the journal Cancer Discovery.

Rhabdomyosarcoma is the most common soft-tissue sarcoma in children and affects muscles in any part of the body.

Among patients diagnosed with non-metastasized disease, about 80 percent survive at least five years, although they may experience substantial treatment-related toxic effects. However, for those with metastatic disease, the five-year survival rate is about 30 percent even with aggressive treatment.

NCI’s effort to characterize the genetic events that contribute to rhabdomyosarcoma was led by Javed Khan, M.D., head of the Oncogenomics Section, Pediatric Oncology Branch, Center for Cancer Research, and Jack Shern, M.D., a clinical fellow.

“These studies are very difficult to do because tissue acquisition and validation is so complex,” said Khan. “It must be noted therefore that this work would not have been possible without our brave pediatric patients and their families. In the face of their life-threatening disease, they offered their tumors for study knowing that they would not personally benefit from this work but in the hope that investigators might learn lessons that would help children diagnosed with rhabdomyosarcoma in the future.”

Khan’s team used a number of advanced sequencing techniques to investigate the genetic changes in a total of 147 rhabdomyosarcoma tumors which were paired with normal tissue samples.

These sequencing tools allowed them to unravel the complex molecular events that occur in tumor cells, compare normal DNA with tumor DNA, identify mutations in genes, and determine exactly which genes are turned on (activated) or turned off (deactivated), leading to progression of this cancer.

Through their studies, they identified two distinct genotypes of rhabdomyosarcoma tumors. The first genotype is characterized by either a PAX3 or PAX7 fusion gene; a fusion gene is a gene made by joining parts of two different genes.

The second genotype lacks a PAX fusion gene but harbors mutations in key signaling pathways; a signaling pathway is a group of proteins that work together to regulate one or more cell functions, such as cell division or cell death.

The researchers also found that, as in other types of pediatric cancers, the overall number of alterations in tumor DNA that develop over the children’s lifespan (known as somatic mutations) were relatively low compared to DNA alterations that children were born with. The somatic mutation rate was especially low in tumors with a PAX fusion gene.

Nevertheless, they did find relatively frequent somatic mutations in several genes, including NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB, all of which had previously been found to be mutated in rhabdomyosarcoma, as well as the genes FBXW7 and BCOR, which had not been previously associated with this disease.

Moreover, they identified mutations in additional genes in the RAS/PIK3CAsignaling pathway. Overall, alterations in this pathway were found in 93 percent of rhabdomyosarcoma tumors.

Intriguingly, many of the genes mutated in the tumors that did not have a PAX fusion gene were found to be turned on or off by proteins produced by PAX fusion genes.

“Although more work is needed, our study may provide researchers with the rationale to develop genomics-guided therapeutic interventions with greater efficacy and fewer side effects than the treatments options currently available for pediatric patients with rhabdomyosarcoma,” Shern said.

Building on this research, Khan and his team will design and test interventions that target the genetic drivers identified in this genomic analysis of rhabdomyosarcoma.

This research was a collaboration that included the Children’s Oncology Group (which collected and banked the majority of the patient tumor samples used in the study) and the Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Mass. (which provided additional patient tumor samples and bioinformatics support).

NCI has a diverse genomic portfolio, including The Cancer Genome Atlas (TCGA) program which is supported by both NCI and another institute at NIH, the National Human Genome Research Institute.


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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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 TechnologyNetworks.com 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

Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
Tuesday, July 21, 2015
NIH Study Identifies Gene Variant Linked to Compulsive Drinking
Mice carrying the Met68BDNF gene variant would consume excessive amounts of alcohol.
Tuesday, July 21, 2015
In Blinding Eye Disease, Trash-Collecting Cells Go Awry, Accelerate Damage
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Friday, July 03, 2015
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
NCI-MATCH Trial will Link Targeted Cancer Drugs to Gene Abnormalities
Precision medicine trial will open to patient enrollment in July.
Tuesday, June 09, 2015
A New Role for Zebrafish: Larger Scale Gene Function Studies
A relatively new method of targeting specific DNA sequences in zebrafish could dramatically accelerate the discovery of gene function and the identification of disease genes in humans.
Monday, June 08, 2015
NIH Researchers Pilot Predictive Medicine by Studying Healthy People’s DNA
New study sequence the genomes of healthy participants to find “putative,” or presumed, mutations.
Friday, June 05, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Scientists Create Mice with a Major Genetic Cause of ALS and FTD
NIH-funded study provides new platform for testing treatments for several neurodegenerative disorders.
Friday, May 22, 2015
Mice With a Major Genetic Cause of ALS and FTD Created
NIH-funded study provides new platform for testing treatments for several neurodegenerative disorders.
Thursday, May 21, 2015
New Insights into How DNA Differences Influence Gene Activity, Disease Susceptibility
NIH-funded pilot study provides a new resource about variants across the human genome.
Friday, May 08, 2015
Souped-up Remote Control Switches Behaviors On-and-Off in Mice
BRAIN Initiative yields chemical-genetic tool with push-pull capabilities.
Thursday, May 07, 2015
NIH-funded Study Points Way Forward for Retinal Disease Gene Therapy
Benefits for Leber congenital amaurosis peak after one to three years, then diminish.
Tuesday, May 05, 2015
Possible Treatment for Lethal Pediatric Brain Cancer
NIH-funded preclinical study suggests epigenetic drugs may be used to treat leading cause of pediatric brain cancer death.
Tuesday, May 05, 2015
Statement on NIH Funding of Research Using Gene-Editing Technologies in Human Embryos
Researchers modify the gene responsible for a potentially fatal blood disorder using CRISPR/Cas9 technology.
Saturday, May 02, 2015
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Watching a Tumour Grow in Real-Time
Researchers from the University of Freiburg have gained new insight into the phases of breast cancer growth.
Childhood Cancer Cells Drain Immune System’s Batteries
Cancer cells in neuroblastoma contain a molecule that breaks down a key energy source for the body’s immune cells, leaving them too physically drained to fight the disease.
Urine Proteins Point to Early-Stage Pancreatic Cancer
A combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, researchers at the BCI have shown.
Researcher Discovers Trigger of Deadly Melanoma
New research sheds light on the precise trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, pinpointing the precise place in the process where "traveling" cancer turns lethal.
Genetic Tug of War
Researchers have reported on a version of genetic parental control in mice that is more targeted, and subtle than canonical imprinting.
Error Correction Mechanism in Cell Division
Cell biologists have reported an advance in understanding the workings of an error correction mechanism that helps cells detect and correct mistakes in cell division early enough to prevent chromosome mis-segregation and aneuploidy, that is, having too many or too few chromosomes.
How to Become a Follicular T Helper Cell
Uncovering the signals that govern the fate of T helper cells is a big step toward improved vaccine design.
Researchers Resurrect Ancient Viruses
Researchers at Massachusetts Eye and Ear and Schepens Eye Research Institute have reconstructed an ancient virus that is highly effective at delivering gene therapies to the liver, muscle, and retina.
Cell Aging Slowed by Putting Brakes on Noisy Transcription
Experiments in yeast hint at ways to extend life of some human cells.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!