TY - JOUR
T1 - Hedgehog checkpoints in medulloblastoma
T2 - The chromosome 17p deletion paradigm
AU - Ferretti, Elisabetta
AU - Smaele, Enrico De
AU - Marcotullio, Lucia Di
AU - Screpanti, Isabella
AU - Gulino, Alberto
PY - 2005/12
Y1 - 2005/12
N2 - Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesion in medulloblastoma, has recently been identified as a cause of unrestrained Hedgehog signaling. Such a deletion leads to the loss of REN KCTD11, a novel Hedgehog antagonist, thus removing a checkpoint of Hedgehog-dependent events during cerebellum development and tumorigenesis. The disruption of additional Hedgehog modulators that map to 17p suggests a rationale for a multitargeted therapeutic strategy aimed at interrupting the cooperative activation of the Hedgehog pathway.
AB - Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesion in medulloblastoma, has recently been identified as a cause of unrestrained Hedgehog signaling. Such a deletion leads to the loss of REN KCTD11, a novel Hedgehog antagonist, thus removing a checkpoint of Hedgehog-dependent events during cerebellum development and tumorigenesis. The disruption of additional Hedgehog modulators that map to 17p suggests a rationale for a multitargeted therapeutic strategy aimed at interrupting the cooperative activation of the Hedgehog pathway.
UR - http://www.scopus.com/inward/record.url?scp=28244467388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28244467388&partnerID=8YFLogxK
U2 - 10.1016/j.molmed.2005.10.005
DO - 10.1016/j.molmed.2005.10.005
M3 - Article
C2 - 16290230
AN - SCOPUS:28244467388
VL - 11
SP - 537
EP - 545
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
SN - 1471-4914
IS - 12
ER -