Down syndrome, also known as trisomy 21, is among the most common genetic disorders in humans. It is characterized by duplication of the 21st chromosome. Children with Down syndrome have increased risk of blood and bone marrow cancers such as leukemia. However, brain tumors in these children are relatively rare, a fact once attributed to the shorter life span of Down syndrome patients. More recent studies suggest that certain genes, known to suppress tumor development or growth and thus called tumor suppressor genes, are present on the duplicated chromosome and that the extra copy may be inhibiting solid tumor formation.
Danielpour and colleagues report a 3-year-old boy with an ependymoma, a brain tumor believed to arise from the thin layer of cells that lines the ventricles of the brain and the central canal of the spinal cord. Only two other cases of ependymoma have been reported in individuals with Down syndrome, according to the study. The tumor was found to have a particular molecular alteration—a RELA fusion—commonly associated with a very aggressive behavior in pediatric and young adult patients. This is the first time a RELA fusion-positive tumor has been reported in a patient with Down syndrome, Danielpour said.
Furthermore, the tumor had a high expression of OLIG2, a developmental gene not usually present in ependymomas. However, OLIG2 resides on the 21st chromosome, the one duplicated in people with Down syndrome, a fact that could alter how the gene behaves. Danielpour and colleagues hypothesize that this fact could account for the particularly aggressive nature of the tumor, which in this case recurred rapidly after it had been surgically removed.
“OLIG2 has a role in the growth of new and abnormal blood vessels in solid tumors,” said Danielpour, associate professor of Neurosurgery. “Tumors that have a high expression of this marker may be less responsive to certain cancer drugs.”
Further research into the role of OLIG2 in tumor behavior is needed, which could yield new options for medical management of these tumors in the future, he added. In general, ependymomas are not very responsive to chemotherapy, and if they cannot be surgically removed or recur, patients often do not have good treatment options. “Our ability to choose the right drugs and predict response to the drugs has improved through what we are learning about genes and the proteins that they produce,” Danielpour said. “We hope that in the future this will lead to better options, better treatments and less guesswork.”