Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New gene-sequencing tools offer clues to highest-risk form of a childhood cancer

03.12.2012
New gene-sequencing tools offer clues to highest-risk form of a childhood cancer

2 gene mutations I.D.'d in neuroblastoma, says researcher from the Children's Hospital of Philadelphia

Using powerful gene-analysis tools, researchers have discovered mutations in two related genes, ARID1A and ARID1B, that are involved in the most aggressive form of the childhood cancer neuroblastoma. While these findings do not immediately improve clinical treatments, they identify a novel pathway that is defective in these cancers, a pathway that scientists can now study to develop potential new therapies.

"These gene alterations were not previously known to be mutated in neuroblastoma, and they may significantly advance our knowledge of the underlying biological pathways that drive this disease," said study leader Michael D. Hogarty, M.D., a pediatric oncologist at The Children's Hospital of Philadelphia. "These two genes function in a group of genes that seems to play an important role in neural cell behavior, and we will now work to discover if this insight may open up new treatments for children with tumors having these mutations."

Hogarty, along with Victor Velculescu, M.D., Ph.D., of the Johns Hopkins Kimmel Cancer Center, co-led the study that appeared today in Nature Genetics.

The scientists received over $1 million in funding from the St. Baldrick's Foundation, a volunteer-driven and donor-centered charity dedicated to raising money for childhood cancer research.

The current study employed sophisticated next-generation sequencing technology that identified the entire DNA sequence for a set of neuroblastoma tumors. "When this project started, it was the first of its kind to focus on a childhood tumor," said Hogarty. "This is important, because cataloguing all the DNA mutations in neuroblastoma, or any tumor, will allow us to better understand the enemy, and ultimately to make better treatment decisions."

Striking the peripheral nervous system, neuroblastoma usually appears as a solid tumor in the chest or abdomen of young children. It accounts for 7 percent of all childhood cancers, but 10 to 15 percent of all childhood cancer-related deaths.

In the current study, Hogarty and colleagues identified alterations in two genes, ARID1A and ARID1B, neither of which had previously been reported to be involved in neuroblastoma. Both genes are thought to affect chromatin, a combination of DNA and protein that regulates the activities of genes and ultimately controls the behavior of a cell. During normal development, neural cells switch from a primitive, rapidly dividing state (neuroblasts) into a more differentiated, or mature state (neurons).

However, said Hogarty, mutations in ARID1A and ARID1B may prevent this orderly transition, keeping the neural cells in the uncontrolled stage of growth that becomes a cancerous tumor. "Unfortunately, children with these mutations have a particularly aggressive, treatment-resistant form of neuroblastoma," he added. The current study found that ARID1A and ARID1B mutations occur in 5 to 15 percent of high-risk neuroblastomas, but the pathway these genes affect may have a broader role in the disease—a possibility that Hogarty and colleagues plan to investigate further. It is possible that children having tumors with these mutations will receive more aggressive or more experimental treatments in the future.

Ultimately, said Hogarty, studies of the pathway affected by these genes may lay the foundation for future targeted therapies aimed at this pathway.

In the current study, the scientists also developed an approach that detects the tumor DNA abnormalities in the blood. "All tumors harbor genetic mistakes that leave a fingerprint in the DNA, and tumor DNA is often detected in the blood as well," he explained. "We may be able to develop a blood test, personalized to each cancer patient, to detect their tumor fingerprint in circulating blood DNA. This would permit oncologists to more accurately monitor patients for treatment response and recurrence, and offer a tool to help guide treatment decisions."

In addition to funding from St. Baldrick's, this study also received support from the National Institutes of Health (grant CA121113), the Children's Oncology Group, the Virginia and D.K. Ludwig Fund for Cancer Research, Swim Across America, and the AACR Stand Up to Cancer-Dream Team Translational Cancer Research Grant.

"Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma," Nature Genetics, advance online publication, Dec. 2, 2012. doi: 10.1038/ng.2493

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 516-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

Rachel Salis-Silverman | EurekAlert!
Further information:
http://www.chop.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>