The group 3 subtype accounts for about 25 percent of medulloblastoma cases and usually occurs in infants and toddlers. About half of group 3 patients are alive five years after diagnosis, which makes group 3 the subtype with the worst prognosis.
In contrast, about 75 percent of patients with SHH medulloblastoma become long-term survivors. The SHH subtype is named for the SHH signaling pathway, which is abnormally activated in tumor cells. About 30 percent of medulloblastoma patients, usually children less than 3 years old and adults, have the SHH subtype.
Researchers have identified a protein interaction that is a hallmark of an aggressive subtype of medulloblastoma and that may provide a new treatment strategy. The research appears today in the scientific journal Cancer Cell.
The results also answer a question that has puzzled researchers: Why the proteins Myc and MycN, which were generally considered to be interchangeable, lead to two distinct subtypes of medulloblastoma when overexpressed in developing neurons. The subtypes - group 3 and sonic hedgehog (SHH) - are among four that make up medulloblastoma, the most common malignant childhood brain tumor.
Working in genetically engineered mice, researchers showed that the Miz1 protein plays a pivotal role in determining tumor identity. Investigators demonstrated that is because Miz1 binds effectively with Myc but not MycN. The resulting Myc-Miz1 complex binds to DNA, altering gene expression to drive the growth and spread of group 3 medulloblastoma rather than the SHH or other subtypes.