The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project has identified the most common genetic alteration ever reported in the brain tumor ependymoma and the evidence that the alteration drives tumor development.
The research is published in the journal Nature.
The results provide a foundation for new research to improve diagnosis and treatment of ependymoma, the third most common brain tumor in children.
The disease remains incurable in 40% of young patients.
The newly discovered alteration involves a gene named RELA. The gene plays a pivotal role in the NF-κB pathway, a signaling system in cells that regulates inflammation. Researchers have long recognized that this pathway is inappropriately switched on in many adult tumors.
In this study, 70% of young patients with ependymomas in the front part of the brain carried the RELA alteration and few other genetic changes. The alteration was not found in ependymomas in other regions of the brain.
The alteration fuses RELA with parts of another gene, C11orf95, in a process called translocation. The translocation produces abnormal proteins that rapidly cause fatal brain tumors in mice. These tumors resembled the human disease.
St. Jude is now leading an international study to determine if the C11orf95-RELA translocation might help predict the outcome for ependymoma patients. An analytic tool called CICERO developed by St. Jude researchers played a key role in identifying the translocation.
Finding the translocation required sifting through 246 billion pieces of genetic information that contain the complete genetic code of the tumor as well as the normal DNA from 41 young patients with ependymoma.
The researchers also studied the RNA in 77 ependymomas. Using CICERO, researchers found abnormalities in RNA that led them to the C11orf95-RELA translocation.
The fusion gene was created when a piece of chromosome 11 that houses both the C11orf95 and RELA genes was shattered and incorrectly reassembled.
Of the 41 ependymomas in this study that began in the front part of the brain, 29 tumors had the translocation and made RELA fusion proteins.
Researchers are working to understand how the fusion proteins cause cancer. Evidence suggests that C11orf95 plays a key role by altering the way that RELA moves through the cell and performs its normal functions. Investigators also discovered translocations involving other genes that appear to drive ependymoma. ( Xagena )
Source: St. Jude Children's Research Hospital, 2014