Navigation Links
Tumors evolve rapidly in a childhood cancer, leaving fewer obvious tumor targets
Date:1/20/2013

An extensive genomic study of the childhood cancer neuroblastoma reinforces the challenges in treating the most aggressive forms of this disease. Contrary to expectations, the scientists found relatively few recurrent gene mutationsmutations that would suggest new targets for neuroblastoma treatment. Instead, say the researchers, they have now refocused on how neuroblastoma tumors evolve in response to medicine and other factors.

"This research underscores the fact that tumor cells often change rapidly over time, so more effective treatments for this aggressive cancer will need to account for the dynamic nature of neuroblastoma," said study leader John M. Maris, M.D., director of the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia (CHOP).

Striking the peripheral nervous system, neuroblastoma usually appears as a solid tumor in a young child's chest or abdomen. It comprises 7 percent of all childhood cancers, but causes 10 to 15 percent of all childhood cancer-related deaths. Neuroblastoma is notoriously complex, with a broad number of gene changes that can give rise to the disease.

Maris headed the multicenter research collaborative, the TARGET (Therapeutically Applicable Research to Generate Effective Treatments) initiative, which released its findings today in Nature Genetics. This largest-ever study genomic study of a childhood cancer analyzed DNA from 240 children with high-risk neuroblastomas. Using a combination of whole-exome, whole-genome and transcriptome sequencing, the study compared DNA from tumors with DNA in normal cells from the same patients.

Researchers at CHOP and other centers previously discovered neuroblastoma-causing mutations, such as those in the ALK gene. In the subset of patients carrying this mutation, oncologists can provide effective treatments tailored to their genetic profile.

"A few years ago, we thought we would be able to sequence the genomes of individual patients with neuroblastoma, detect their specific cancer-causing mutations, and then select from a menu of treatments," said Maris. The oncology researchers designed the TARGET study to perform genomic analyses of a large cohort of high-risk neuroblastoma patients, with the goal of mapping out a limited number of treatment strategies. This approach would represent a significant step forward in personalizing neuroblastoma therapy.

However, while the researchers confirmed that roughly 10 percent of the study's neuroblastoma patients had ALK mutations, and found that a handful of other gene mutations each accounted for percentages in the single digits, there were relatively few recurrent mutations in somatic (non-germline) cells. "The relative paucity of recurrent mutations challenges the concept that druggable targets can be defined in each patient by DNA sequencing alone," wrote the authors.

In the absence of frequently altered oncogenes that drive high-risk neuroblastomas, the authors concluded that most such cases may result from other changes: rare germline mutations, copy number variations and epigenetic modifications during tumor evolution.

"Personalized medicine is more complex than we had hoped," said Maris. "While there are successes such as those in treating patients whose tumors harbor ALK mutations, this study implies that we must think very differently about how we'll use genomics to define treatment." Maris added that neuroblastoma researchers may need to turn to functional genomics, learning which tumors will or won't respond to treatments, as well as going beyond a static picture of a cancer cell with fixed genetic contents, to devising interventions to deal with dynamic tumor cells that evolve during nervous system development.


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

Related biology news :

1. Nanotherapy: Treating deadly brain tumors by delivering big radiation with tiny tools
2. TGen leads new National Institutes of Health study of brain tumors
3. A single stem cell mutation triggers fibroid tumors
4. Cancerous tumors deliver pro-metastatic information in secreted vesicles
5. Breast cancer drug could halt other tumors
6. Researchers identify proteins that indicate which kidney tumors are most likely to spread
7. Cancer stem cells isolated from kidney tumors
8. Study uncovers mechanism used by BRCA1 to suppress tumors
9. Leading evolutionary scientist to discuss how genome of bacteria has evolved
10. Excessive worrying may have co-evolved with intelligence
11. Hitting snooze on the molecular clock: Rabies evolves slower in hibernating bats
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/4/2017)... Oct. 4, 2017  GCE Solutions, a global clinical research organization ... document anonymization solution on October 4, 2017. Shadow is designed to ... comply with policy 0070 of the European Medicines Agency (EMA) in ... ... ...
(Date:6/30/2017)... , June 30, 2017 Today, ... developer and supplier of face and eye tracking ... Featured Product provider program. "Artificial ... innovative way to monitor a driver,s attentiveness levels ... from being able to detect fatigue and prevent ...
(Date:5/16/2017)... 2017  Veratad Technologies, LLC ( www.veratad.com ), an ... identity verification solutions, announced today they will participate as ... 15 thru May 17, 2017, in Washington ... Center. Identity impacts the lives of ... quickly evolving digital world, defining identity is critical to ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... , Oct. 11, 2017  VMS BioMarketing, a leading provider ... nationwide oncology Clinical Nurse Educator (CNE) network, which will launch ... for communication among health care professionals to enhance the patient ... office staff, and other health care professionals to help women ... cancer. ...
(Date:10/11/2017)... Bay, Florida (PRWEB) , ... October 11, 2017 ... ... and Drug Administration (FDA) has granted orphan drug designation to SBT-100, its novel ... (sdAb) for the treatment of osteosarcoma. SBT-100 is able to cross the cell ...
(Date:10/10/2017)... ... October 10, 2017 , ... Dr. Bob Harman, founder and CEO ... Diego Rotary Club. The event entitled “Stem Cells and Their Regenerative ... attendees. Dr. Harman, DVM, MPVM was joined by two human doctors: Peter B. ...
(Date:10/10/2017)... PA (PRWEB) , ... October 10, 2017 , ... ... year’s recipients of 13 prestigious awards honoring scientists who have ... presented in a scheduled symposium during Pittcon 2018, the world’s leading conference and ...
Breaking Biology Technology: