Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deleted genes help predict outcome in a children’s cancer

24.11.2005


Genetic clues guide customized treatment for neuroblastoma



A new study reports that a loss of genes on chromosome 1 or chromosome 11 raises the risk of death from the children’s cancer neuroblastoma, even when other indicators seem to point to a lower-risk form of the disease. This research finding will help guide physicians to the most appropriate treatment for the cancer, which strikes the peripheral nervous system. The approach used may also be applied to customizing care for other cancers.

"Identifying more accurate risk levels of this cancer allows doctors to treat aggressive types of the cancer appropriately, while not subjecting children with lower-risk cancer to overtreatment," said study leader John Maris, M.D., of The Children’s Hospital of Philadelphia. The study from the Children’s Oncology Group, a cooperative research organization of pediatric cancer centers, appears in the November 24 New England Journal of Medicine.


The research team analyzed tumor samples from 915 children with neuroblastoma. Neuroblastoma is the most common cancer in infants, accounting for 10 percent of all pediatric cancers, but its course is not easily predictable. Often occurring as a solid tumor in a child’s abdomen or chest, some cases spontaneously resolve even without surgery, while others are particularly aggressive -- resisting initial therapy, or causing a relapse. The more accurately physicians can identify a patient’s risk level at the initial evaluation, the better they can customize treatment to each child.

Turning the Tide of Pediatric Cancers Using details of tumor biology to help classify a patient’s prognosis – a process called risk stratification – has received a large boost from the flood of genetic data from the National Genome Project. At the same time, researchers are translating knowledge of molecular events and biological processes into experimental cancer treatments.

As with all science, findings such as the current study of chromosome deletions in neuroblastoma are incremental advances. Those advances occur against the backdrop of a remarkable turnaround: in one generation, survival rates for pediatric cancer have risen from roughly 25 percent in the 1970s to nearly 80 percent today.

One major reason for the dramatic progress in pediatric survival rates is the fact that, over the years, high percentages of children with cancer have participated in clinical trials of new treatments. Today, as researchers work to counteract the most refractory and aggressive cancers, the new treatments are often targeted therapies-- specific agents that attack cancer cells while sparing healthy cells. One such treatment used at Children’s Hospital is a compound called MIBG that selectively concentrates in neuroblastoma cells. When bound to a radioactive isotope of iodine and delivered by an I.V. line, the radioactive package kills cancer cells, with low toxicity to healthy tissue.

"These treatments are not cures, but they are bringing us closer to controlling neuroblastoma," says Dr. Maris. "Our goal is to successfully treat the cases that have learned to resist therapy."

Minding P’s and Q’s in Two Chromosomes Guides Treatment Decisions The current study builds on a foundation of decades of research into neuroblastoma at The Children’s Hospital of Philadelphia and other pediatric cancer centers. Pediatric oncologists have known for some time that amplification, an abnormal increase in the number of copies, of a cancer-causing gene called MYCN heralds a high-risk, aggressive form of neuroblastoma. However, some 60 percent of high-risk neuroblastoma tumors do not show MYCN amplification, suggesting that other biological pathways are operating.

Based on previous studies by Dr. Maris and other researchers that identified abnormalities on chromosomes 1 and 11 as contributing to high-risk neuroblastoma, the current research team analyzed gene defects in a large series of neuroblastoma tumors. "We found that loss of genetic material on chromosome bands 1p36 and 11q23 was strongly linked to high-risk neuroblastoma," he said. He added that the survival rate was worse when the loss of material was unbalanced on chromosome 11, occurring on the chromosome’s "q" arm but not on its shorter "p" arm.

Scientists call this deletion of one copy of a chromosome "loss of heterozygosity" (LOH). The unbalanced 11q LOH and the 1p36 LOH were independent markers of worse outcome for patients, regardless of other prognostic clues. For instance, unbalanced 11q LOH occurs almost always in tumors not showing amplified copies of the MYCN gene.

"Children known to have MYCN amplification are more likely to already be receiving the most aggressive therapy," said Dr. Maris. "However, it is important to look for 1p36 LOH and unbalanced 11q LOH in children with localized disease without MYCN amplification. Patients having one or both of these deletions may benefit from more intensive early treatment such as chemotherapy. If we can correctly detect risk factors at diagnosis, we can tailor their treatment accordingly."

Based on these findings, the Children’s Oncology Group plans to add the status of chromosome arms 1p and 11q to its list of prognostic markers in evaluating children with neuroblastoma. This information will be incorporated into future clinical trials, as researchers analyze new treatments for this pediatric cancer. "As we continue to develop better treatments, we hope to combine those treatments with more refined diagnoses, so we can identify and then treat high-risk cancers earlier, before they can progress or relapse," says Dr. Maris.

The research team will be conducting further work on these particular genetic abnormalities. "Our hope is to identify one or more genes on chromosome arm 11q that are involved in the development of aggressive neuroblastoma, and then use those specific genes as targets for therapy," said lead author Edward F. Attiyeh, M.D., also of The Children’s Hospital of Philadelphia.

The researchers also look toward broader implications in their research. "What we have achieved in this pediatric cancer is applicable to other cancers," said Dr. Maris. "This example of molecular medicine is a step in the direction of using powerful genomic technologies to individualizing care."

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

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>