@article{ed5a231c44dc4729b850a87f110da2d8,
title = "Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells",
abstract = "Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedgehog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblastoma by 3 months of age. Shh pathway activation in stem cells promotes stem cell proliferation but only causes tumors after commitment to-and expansion of-the neuronal lineage. Notably, tumors initiated in stem cells develop more rapidly than those initiated in progenitors, with all animals succumbing by 3-4 weeks. These studies suggest that medulloblastoma can be initiated in progenitors or stem cells but that Shh-induced tumorigenesis is associated with neuronal lineage commitment.",
keywords = "CELLBIO, HUMDISEASE, STEMCELL",
author = "Yang, {Zeng Jie} and Tammy Ellis and Markant, {Shirley L.} and Read, {Tracy Ann} and Kessler, {Jessica D.} and Melissa Bourboulas and Ulrich Sch{\"u}ller and Robert Machold and Gord Fishell and Rowitch, {David H.} and Wainwright, {Brandon J.} and Wechsler-Reya, {Robert J.}",
note = "Funding Information: The authors thank Susan Su, Pate Skene, and the NIH Neuroscience Microarray Consortium for help with laser capture and microarray analysis; Simon Lin at Northwestern University for assistance with bioinformatics; Beth Harvat and Mike Cook for flow cytometry; and Jack Dutton, Mark Johnson, and Zhen Zhao for assistance with animal colony maintenance. T.E. is a John Trivett Senior Research Fellow. This work was supported by funds from the National Health and Medical Research Council of Australia (B.J.W.), the ARC Special Research Centre for Functional and Applied Genomics (B.J.W.), the Queensland Cancer Fund (B.J.W.), the Hope Street Kids Foundation (Z.-J.Y.), the Kislak-Sussman Fund (R.J.W.-R.), the Children's Brain Tumor Foundation (R.J.W.-R.), the Pediatric Brain Tumor Foundation (R.J.W.-R.), the McDonnell Foundation (R.J.W.-R.), the Australian Cancer Research Foundation, and NINDS grant number NS052323-01 (R.J.W.-R.). ",
year = "2008",
month = aug,
day = "12",
doi = "10.1016/j.ccr.2008.07.003",
language = "English (US)",
volume = "14",
pages = "135--145",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}
