Medulloblastoma is the most common malignant pediatric brain tumor. There are four molecular subgroups: SHH, WNT, group 3 and group 4. Research has already revealed which neural tissues give rise to SHH and WNT. But it was less clear where group 3 and group 4 medulloblastoma come from.
Scientists at St. Jude had comprehensive molecular datasets on medulloblastoma. Researchers at Seattle Children’s had the first map of cells in part of the human brain called the cerebellum. The St. Jude scientists compared their data to the map. The results showed that group 3 and group 4 medulloblastoma come from a neural structure called the rhombic lip.
“There has existed this ambiguity and overlap between group 3 and group 4 that made it challenging to resolve their origins,” said Paul Northcott, PhD, St. Jude Developmental Neurobiology. “We’ve had evidence that these groups had some kind of common ancestry that then likely diverged depending on the genetic events driving those tumors, but we couldn’t say that definitively until now.”
The study reveals that group 3 and group 4 come from different populations of cells in the rhombic lip. The rhombic lip is a part of the developing cerebellum. Group 3 cells are more primitive whereas group 4 cells are further along in their development.
This knowledge may lead to better models for studying these subgroups. Additionally, knowing the cell of origin may reveal new therapeutic opportunities for subgroups of medulloblastoma that are often the most clinically challenging.
The findings appeared in Nature.