Navigation Links
Researchers find gene location that gives rise to neuroblastoma, an aggressive childhood cancer
Date:5/7/2008

Using advanced gene-hunting technology, an international team of researchers has for the first time identified a chromosome region that is the source of genetic events that give rise to neuroblastoma, an often fatal childhood cancer.

The investigators found that the presence of common DNA variations in a region of chromosome 6 raises the risk that a child will develop a particularly aggressive form of neuroblastoma, a cancer of the peripheral nervous system that usually appears as a solid tumor in the chest or abdomen. Neuroblastoma accounts for 7 percent of all childhood cancers, but due to its aggressive nature, causes 15 percent of all childhood cancer deaths.

Until now we had very few clues as to what causes neuroblastoma, said pediatric oncologist John M. Maris, M.D., who led the study at The Childrens Hospital of Philadelphia, where he is the director of the Center for Childhood Cancer Research. Although there is much work to be done, added Maris, understanding this cancers origin provides a starting point for developing novel treatments. The study team reported its findings in todays Online First version of the New England Journal of Medicine.

Neuroblastoma is the most common solid cancer of early childhood and has long been known to include subtypes that behave very differently. Some cases strike infants but spontaneously disappear with minimal treatment, while other cases in older children may be relentlessly aggressive from the start.

Researchers at Childrens Hospital and colleagues in the multicenter Childrens Oncology Group have for decades analyzed tumors for characteristics such as amplified levels of a cancer-causing gene and deletions of chromosome material. They used those tumor peculiarities to classify neuroblastoma into risk levels that guide oncologists toward the most appropriate treatments. Properly defining risk level helps us to avoid the twin pitfalls of undertreating or overtreating any given child with neuroblastoma, added Maris.

However, little was known about genetic events that predispose a child to developing a neuroblastoma tumor. In roughly half of neuroblastoma cases, the cancer is not discovered until it has spread widely in a patients body, so understanding how a tumor originates may allow oncologists to design earlier and more successful interventions.

In the current study, Mariss team collaborated with Hakon Hakonarson, M.D., Ph.D., director of Childrens Hospitals Center for Applied Genomics, to analyze blood samples from approximately 1,000 neuroblastoma patients, as well as samples from some 2,000 healthy children recruited through the Childrens Hospital network. A DNA chip analysis performed at the genome center identified three single nucleotide polymorphisms (SNPs)changes in single bases on the DNA helix. Out of over 550,000 SNPs studied, those SNPs were much more common in patients with neuroblastoma, compared to the controls. The three SNPs occurred together on a band of chromosome 6 designated 6p22.

The researchers repeated the analysis in blood samples from additional groups of patients and control subjects from the U.S. and the U.K., and confirmed their finding that variants in the 6p22 region were implicated in neuroblastoma. There are two genes in the 6p22 region, but their functions are largely unknown.

We are doing further studies to understand how these relatively common genetic changes translate into increased risk of cancer, said Maris. Ultimately, they probably cause subtle changes in gene expression during early development, interacting with other genes yet to be discovered. This suggests that neuroblastoma has complex causes, in which a series of genetic changes may occur at different sites to combine into a perfect storm that results in this cancer.

The researchers found that patients with these at-risk SNPs on chromosome 6 were more likely to develop aggressive neuroblastoma. The initial changes on chromosome 6 in all their body cells eventually led to the genetic abnormalities seen in tumor cells in high-risk forms of the disease.

Because their finding reveals only the first step in a series of molecular events, added Maris, it would be premature to do prenatal genetic testing for the SNPs on chromosome 6. His research team will continue to perform genetic analyses, in search of other gene changes that interact with those SNPs. One data source will be 5,000 tissue samples in Mariss labthe worlds largest collection of neuroblastoma samples, drawing on decades of research into the disease by Maris, his colleagues and predecessors at Childrens Hospital.

This discovery lays the foundation for learning how these initial changes influence biological pathways that lead to neuroblastoma, added Maris. Understanding those pathways may guide us to new and better therapies that precisely target this cancer. Hakonarson added, This study represents one of many ongoing projects to which scientists at The Childrens Hospital of Philadelphia are committed, and we anticipate several comparable discoveries will be made in other common and equally complex pediatric disorders, such as autism, asthma, ADHD and diabetes.


'/>"/>

Contact: Rachel Salis-Silverman
Salis@email.chop.edu
267-426-6063
Children's Hospital of Philadelphia
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... , ... PawPaws brand pet supplements owned by Whole Health Supply ... health of felines. The formula is all-natural and is made from Chinese herbs that ... Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract and Rehmannia Root ...
(Date:6/25/2016)... ... ... of Bruton Memorial Library on June 21 due to a possible lice infestation, as reported ... head lice: the parasite’s ability to live away from a human host, and to infest ... in the event that lice have simply gotten out of control. , As lice are ...
(Date:6/25/2016)... ... ... On Friday, June 10, Van Mitchell, Secretary of the Maryland Department of Health ... of their exemplary accomplishments in worksite health promotion. , The Wellness at Work Awards ... at the BWI Marriott in Linthicum Heights. iHire was one of 42 businesses to ...
(Date:6/24/2016)... PASADENA, CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. ... he would lash out at his family verbally and physically. , “When something upset him, ... table, he would use it. He would throw rocks at my other children and say ...
(Date:6/24/2016)... ... , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business ... to $12 an hour by 2020 and then adjusting it yearly to increase at the ... minimum wage, assure the wage floor does not erode again, and make future increases more ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... VIEW, Calif. , June 23, 2016 ... a.m. CST on Thursday, July 7, 2016 , , , ... kayla.belcher@frost.com ) , , , , EXPERT PANELISTS:  , ... Nitin Naik; Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa ... The global pharmaceutical industry is witnessing an ...
(Date:6/23/2016)... 2016  Guerbet announced today that it has been ... Award . One of 12 suppliers to ... its support of Premier members through exceptional local customer ... commitment to lower costs. ... our outstanding customer service from Premier," says Massimo ...
(Date:6/23/2016)... June 23, 2016 The Biotechnology ... continues to present great opportunities to investors. Stock-Callers.com assesses ... Intrexon Corp. (NYSE: XON ), Vertex Pharmaceuticals ... (NASDAQ: ARNA ), and Regeneron Pharmaceuticals Inc. ... stocks and receive your complimentary trade alerts at: ...
Breaking Medicine Technology: