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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Researchers invent tiny, light-powered wires to modulate brain's electrical signals

21.02.2018 | Life Sciences

The “Holy Grail” of peptide chemistry: Making peptide active agents available orally

21.02.2018 | Life Sciences

Atomic structure of ultrasound material not what anyone expected

21.02.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>