Cancer begins when a cell goes rogue—mutating its DNA, dividing uncontrollably. Learning what type of cell starts a particular cancer—the “cell of origin”—is extremely valuable, providing insights into tailored therapies that are most likely to work.
New research led by a St. Jude scientist has pinpointed likely cells of origin for a common childhood brain tumor, Group 4 medulloblastoma. The cells come from a part of the cerebellum called the upper rhomic lip.
Finding the cells wasn’t simple. The scientists extensively studied 28 tumor samples from children with medulloblastoma, surveying each tumor for details about how its genes are turned on and off. Specifically, they analyzed the tumors’ epigenome, an array of molecules that covers the surface of DNA and helps regulate gene activity, acting like a control switch to decide which genes are active or inactive in the cell.
Using computational methods, they used this data to reconstruct networks of proteins called transcription factors. These networks determine which type of medulloblastoma a tumor becomes. This work led to identification of the likely Group 4 tumor cells of origin, and also yielded insights for other subtypes of the disease.
“The findings open new therapeutic avenues, particularly for the Group 3 and 4 subtypes, where patient outcomes are inferior for the majority of affected children,” said Paul Northcott, PhD, of St. Jude Developmental Neurobiology. The results were published in the journal Nature.