Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Gene Sequencing Project Mines Data Once Considered 'Junk' for Clues about Cancer

Published: Monday, January 28, 2013
Last Updated: Monday, January 28, 2013
Bookmark and Share
St. Jude Children’s Research Hospital takes new approach to measuring the repetitive DNA at the end of chromosomes and opens new window on mechanisms fueling cancer.

Genome sequencing data once regarded as junk is now being used to gain important clues to help understand disease. The latest example comes from the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project, where scientists have developed an approach to mine the repetitive segments of DNA at the ends of chromosomes for insights into cancer.

These segments, known as telomeres, had previously been ignored in next-generation sequencing efforts. That is because their repetitive nature meant that the resulting information had defied analysis and the data were labeled as junk. But researchers have now traced changes in the volume of telomeric DNA to particular types of cancer and their underlying genetic mistakes. Investigators found that 32 percent of pediatric solid tumors carried extra DNA for telomeres, compared to just 4 percent of brain tumors and none of the leukemia samples studied. The findings were published recently in the journal Genome Biology.

Using this new approach, the investigators have linked changes in telomeric DNA to mutations in the ATRX gene and to longer telomeres in patients with a subtype of neuroblastoma, a cancer of the sympathetic nervous system. Telomere length limits how many times cells can divide. Mechanisms that maintain or lengthen telomeres contribute to the unchecked cell division that is a hallmark of cancer.

“This paper shows how measuring the DNA content of telomeres can enhance the value of whole- genome sequencing,” said Matthew Parker, Ph.D., the paper’s first author and a St. Jude postdoctoral fellow. “In the case of the ATRX mutation, the telomere findings gave us information about the mutation’s impact that would have been hard to get through other means.”

The results stem from the largest study yet of whole-genome sequencing to measure the content of telomeric DNA. The effort involved whole-genome sequencing of normal and tumor DNA from 235 pediatric patients battling 13 different cancers. For comparison, normal DNA from 13 adult cancer patients was included in the research.

“There’s been a lot of interest among cancer researchers into telomere length,” said Richard Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis. “While more research remains, we think it’s important to begin to characterize the genetic sequences that make up the telomeres. That’s a crucial first step to understanding more precisely any role they may play in cancer.”

The Pediatric Cancer Genome Project sequenced the complete normal and cancer genomes of more than 600 children and adolescents with some of the most aggressive and least understood cancers. Investigators believe the project’s findings will lay the foundation for a new generation of clinical tools. Despite advances, cancer remains the leading cause of death by disease of U.S. children age 1 and older.

The human genome is stored in the four-letter chemical alphabet of DNA, a molecule that stretches more than 3 billion characters in length and provides the instructions for building and sustaining life. Those instructions are the genes that are organized into the 46 chromosomes found in almost every cell.

Each chromosome ends with the same six-letter DNA sequence that is associated exclusively with telomeres. The DNA sequence does not vary, but the number of times it is repeated does, affecting the length of the telomeres. Telomeres shorten each time cells divide, which explains why their length declines naturally with age.

Researchers have known cancer cells use several mechanisms to circumvent the process and keep dividing. But until now the repetitive nature of the telomeric DNA sequence meant they had little to offer researchers using whole-genome sequencing to map the human genome. Other genes can be assigned to a particular spot on a particular chromosome; telomeres cannot.

“For scientists analyzing whole-genome sequencing data the telomeres were just a headache,” said the study’s corresponding author Jinghui Zhang, Ph.D., an associate member of the St. Jude Department of Computational Biology. “We could not properly map them to a position on the human genome, so we didn’t really use them.”

Then listening to a colleague’s presentation, Parker had an idea: “Why not just count the telomeric DNA and look for changes between the normal and cancer cells of patients?”

Zhang said the question was a conceptual leap in thinking about how to use whole-genome sequencing data to study telomeres and cancer. “This is the classic story of how one person’s problem is another person’s gold,” she said.

Parker and his colleagues developed an approach that correctly distinguished between older and younger individuals based on the amount of telomeric DNA in their blood or bone marrow cells. Researchers used three other methods to confirm that whole-genome sequencing could be used to reliably capture telomeric DNA differences between normal and cancer cells. Additional supportive evidence came when investigators found that the method yielded similar estimates of the telomeric DNA content of twins with leukemia who shared similar genetic alterations.

When investigators used the method to study pediatric cancer patients, they found tumors that gained telomeric DNA were also more likely to contain chromosomal abnormalities, including rearrangements within and between chromosomes. Researchers also found that different cancers had distinct patterns of telomeric DNA change. In some cases, the change offered clues about the mechanism responsible for lengthening the telomeres, pointing to a process called alternative lengthening of telomeres.

The other authors are Xiang Chen, Armita Bahrami, James Dalton, Michael Rusch, Gang Wu, John Easton, Michael Dyer, Charles Mullighan, Richard Gilbertson, Suzanne Baker, Gerard Zambetti, David Ellison and James Downing, all of St. Jude; Nai-Kong Cheung, Memorial Sloan-Kettering Cancer Center, New York; and Elaine Mardis, of The Genome Institute at Washington University, St. Louis.

The research was funded in part by the Pediatric Cancer Genome Project, including Kay Jewelers, a lead partner; a Cancer Center Support Grant (CA021765) from the National Cancer Institute at the National Institutes of Health; the Henry Schueler 41&9 Foundation in conjunction with Partnership4Cures; and ALSAC.


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

Genomic Evolution Of High-Risk Leukemia Traced
Highly sensitive genomic analysis of acute lymphoblastic leukemia cells reveals for the first time how the malignant cells evolve to cause relapse.
Friday, March 20, 2015
Tumor Suppressor Protein Plays Key Role In Maintaining Immune Balance
St. Jude Children’s Research Hospital scientists show that the PTEN tumor suppressor protein is essential for proper regulatory T cell function; discovery offers new focus for improving treatment of autoimmune diseases.
Wednesday, January 21, 2015
Gene Therapy Provides Safe, Long-Term Relief for Patients with Severe Hemophilia B
Gene therapy pioneered by St. Jude Children’s Research Hospital, University College London and the Royal Free Hospital provides men with hemophilia B reliable relief from the bleeding disorder.
Friday, November 28, 2014
Mechanism Offers Promising New Approach for Harnessing the Immune System to fight Cancer
Researchers discover how to unleash the immune system against cancer in mice without triggering autoimmune reactions.
Thursday, August 08, 2013
Gene Identified as a New Target for Treatment of Aggressive Childhood Eye Tumor
St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project findings help solve mystery of retinoblastoma’s rapid growth in work that also yields a new treatment target and possible therapy.
Monday, January 16, 2012
Scientific News
The Changing Tides of the In Vitro Diagnostics Market
With the increasing focus in personalized medicine, diagnostics plays a crucial role in patient monitoring.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Less May Be More in Slowing Cholera Epidemics
Mathematical model shows more cases may be prevented and more lives saved when using one dose of cholera vaccine instead of recommended two doses.
Investigating the Vape
Expert independent review concludes that e-cigarettes have potential to help smokers quit.
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Researchers Discover Synthesis of a New Nanomaterial
Interdisciplinary team creates biocomposite for first time using physiological conditions.
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Flu Remedies Help Combat E. coli Bacteria
Physiologists from the University of Zurich have now discovered why the intestinal bacterium Escherichia coli (E. coli) multiplies heavily and has an inflammatory effect.
Marijuana Genome Unraveled
A study by Canadian researchers is providing a clearer picture of the evolutionary history and genetic organization of cannabis, a step that could have agricultural, medical and legal implications for this valuable crop.
Scroll Up
Scroll Down
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!