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Genetic Code for Children's Brain Cancer Deciphered


The genetic code for the most common type of children’s brain cancer, medulloblastoma, has been deciphered by researchers at the Johns Hopkins Kimmel Cancer Center. One of the most notable findings is that genetic changes in children’s cancers are much different from tumors in adults.

Brain cancer is a leading killer of children with cancer

More children die of brain tumors than from any other type of cancer in young people. Medulloblastoma accounts for 15 to 20 percent of all pediatric brain tumors, according to Children’s Hospital Boston. These tumors are located in the cerebellum, which is the part of the brain that controls balance and other motor functions.

The scientists at Johns Hopkins found that children with medulloblastoma have five- to tenfold fewer cancer-linked alterations in their genomes when compared with adults. According to Victor Velculescu, MD, PhD, associate professor of oncology at the Kimmel Cancer Center, “with fewer alterations, the hope is that it may be easier to use the information to develop new therapies for them.”

Effective therapies are needed. Currently, the use of chemotherapy and radiation results in long-term side effects, including hearing loss, loss of height secondary to the radiation, and endocrine dysfunction from radiating the pituitary gland/hypothalamus. Some children develop secondary tumors 8 to 12 years after radiation treatment.

The expected five-year survival for children with standard risk medulloblastoma is 65 to 80 percent, and 60 percent for high-risk disease. The results in infants are disappointing. In children who relapse, there is no effective curative therapy.

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In the Johns Hopkins study, the scientists sequenced nearly all protein-encoding genes in 22 samples of pediatric medulloblastoma and compared them with normal DNA from each patient. The researchers uncovered an average of 11 mutations in each tumor sample.

Once the scientists had this information, they evaluated another set of 66 medulloblastomas, including some taken from adults, to determine how the mutations changed the proteins made by the genes. They then found that the majority of the mutations collect within a few gene pathways, and one pathway in particular, named “epigenetic,” is of special interest.

Until now, scientists have been puzzled about what may cause medulloblastoma. Research has been focused on examining some of the possible genetic pathways. Now one has been found.

“These epigenetic changes may be more important than we thought in childhood cancers,” according to Will Parsons, MD, PhD, formerly of Johns Hopkins and now an assistant professor at Texas Children’s Cancer Center and Baylor College of Medicine.

Medulloblastomas affect about 400 children per year in the United States. Peak incidence is between the ages of 3 and 8, but it can occur anywhere from the newborn up into adulthood. Common symptoms may include headache (from increased pressure within the brain), vomiting, fatigue, and lethargy. Because the duration of symptoms is usually short, children are typically diagnosed with the flu.

By deciphering the genetic code for the most common type of children’s brain cancer, scientists have opened a door for new therapies. According to Parsons, “any information that allows us to understand a patient’s prognosis or provides clues about therapies that might work best in a patient is crucial and will help us provide better care.”

Children’s Hospital Boston
Parsons DW et al. Science 2010 Dec. 16