A recent study published in Nature Genetics has provided new insights into medulloblastoma, the most common malignant brain tumor in children. Researchers found that the ZIC1 gene can drive similar cancers through different mechanisms depending on the context. The study was led by experts from Baylor College of Medicine, Texas Children’s Cancer Center, University of Toronto, St. Jude Children’s Research Hospital, and Mayo Clinic College of Medicine and Science.
“Medulloblastoma arises from malignant transformation of developing neurons in the cerebellum,” explained Dr. Michael Taylor, co-corresponding author and professor at Baylor and Texas Children’s. He noted that while many driver genes are known, others remain less understood. This study focuses on ZIC1's role in central nervous system development.
The research team examined two types of human medulloblastoma: G4 and SHH. These tumors are believed to originate from a common cell type in the cerebellum but grow due to distinct ZIC1 gene mutations.
“G4 medulloblastoma tumors have ZIC1 mutations that produce proteins that have lost their function," said Dr. Paul A. Northcott, co-corresponding author and principal investigator at St. Jude. "In contrast, SHH medulloblastoma tumors have ZIC1 mutations that produce proteins with a new function."
Taylor highlighted how these findings suggest ZIC1 as a critical developmental regulator both normally and when transformed.
Supporting this notion, researchers discovered that overexpression of ZIC1 promotes malignancy in SHH precursor cells.
Northcott emphasized the implications for treatment development: “Our findings highlight the importance of identifying the correct context before designing an approach to treating each medulloblastoma.”
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