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

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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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

Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Researchers Identify Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Saturday, October 31, 2015
Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Friday, October 23, 2015
Charting Genetic Variation Across the Globe
An international team of scientists has created the world’s largest catalog of human genetic differences in populations around the globe.
Tuesday, October 20, 2015
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Tuesday, October 20, 2015
Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Thursday, October 01, 2015
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.
Thursday, October 01, 2015
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Tuesday, September 29, 2015
Scientific News
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Tardigrade's Are DNA Master Thieves
Tardigrades, nearly microscopic animals that can survive the harshest of environments, including outer space, hold the record for the animal that has the most foreign DNA.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos