1. DDX3X Suppresses the Susceptibility of Hindbrain Lineages to Medulloblastoma.
- Author
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Patmore DM, Jassim A, Nathan E, Gilbertson RJ, Tahan D, Hoffmann N, Tong Y, Smith KS, Kanneganti TD, Suzuki H, Taylor MD, Northcott P, and Gilbertson RJ
- Subjects
- Animals, Brain Neoplasms pathology, Cell Lineage genetics, Gene Expression Regulation, Neoplastic genetics, Genes, Homeobox, Humans, Medulloblastoma pathology, Mice, Mutation genetics, Rhombencephalon metabolism, Rhombencephalon pathology, Wnt Proteins genetics, Brain Neoplasms genetics, DEAD-box RNA Helicases genetics, Hedgehog Proteins genetics, Medulloblastoma genetics
- Abstract
DEAD-Box Helicase 3 X-Linked (DDX3X) is frequently mutated in the Wingless (WNT) and Sonic hedghog (SHH) subtypes of medulloblastoma-the commonest malignant childhood brain tumor, but whether DDX3X functions as a medulloblastoma oncogene or tumor suppressor gene is not known. Here, we show that Ddx3x regulates hindbrain patterning and development by controlling Hox gene expression and cell stress signaling. In mice predisposed to Wnt- or Shh medulloblastoma, Ddx3x sensed oncogenic stress and suppressed tumor formation. WNT and SHH medulloblastomas normally arise only in the lower and upper rhombic lips, respectively. Deletion of Ddx3x removed this lineage restriction, enabling both medulloblastoma subtypes to arise in either germinal zone. Thus, DDX3X is a medulloblastoma tumor suppressor that regulates hindbrain development and restricts the competence of cell lineages to form medulloblastoma subtypes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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