Scientists at St. Jude Children’s Research Hospital have discovered which cells give rise to certain high-risk groups of medulloblastoma. The findings will help researchers better understand the biology of the disease, as well as develop better research models and guide their hunt for therapeutic targets. The findings were published today in Nature.
Medulloblastoma is the most common malignant childhood 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: SHH from the external granule layer (where granule neurons develop) and WNT from the brainstem. However, where group 3 and group 4 medulloblastoma come from was harder to ascertain.
Now, scientists have tracked the developmental beginnings of group 3 and group 4 medulloblastoma to the rhombic lip, a structure present in the early development of the cerebellum. This is the first-time researchers have identified a specific origin for group 3 medulloblastoma and reinforces prior findings about group 4.
“There has existed this ambiguity and overlap between group 3 and group 4 that made it challenging to resolve their origins,” said corresponding author Paul Northcott, Ph.D., St. Jude Department of 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.”
“Having helped discover and describe groups 3 and 4 more than a decade ago, it’s been a burning curiosity for my lab to resolve their developmental biology and figure out whether they share a common ancestry,” Northcott said.
Finding the right road map
In 2019, Northcott and his team published an atlas of mouse cerebellar development. This work relied on single-cell transcriptional profiling and enabled the researchers to compare profiles from medulloblastoma patients to the mouse cerebellum. The previous mouse atlas work suggested that group 4 medulloblastoma originate from unipolar brush cells, which also trace back developmentally to the rhombic lip. But the origins of group 3 medulloblastoma remained murky.
Source: Read Full Article