GLI3 is not mutated commonly in sporadic medulloblastomas.
BACKGROUND
Medulloblastoma is a malignant, invasive embryonic tumor of the cerebellum. Sonic hedgehog (SHH) is a secreted glycoprotein that has a major role in the developing cerebellum. Activation of the SHH pathway resulting from mutations in the PATCH gene, which is an inhibitor of the pathway, are associated with hereditary and sporadic medulloblastomas. The GLI3 protein is another negative regulator of SHH signaling. The authors hypothesized that mutations in GLI3 may be associated with meduloblastomas.


METHODS
The authors describe a patient with hereditary Greig syndrome, which was caused by mutations in GLI3, and medulloblastoma. Another such patient was described in the literature. They also sequenced the GLI3 gene, including all exon-intron boundaries, in an additional 12 sporadic medulloblastomas.


RESULTS
The authors detected a new nonsense germline mutation in a child with Greig syndrome and medulloblastoma. This mutation generates a stop codon in position 809 of GLI3 that has been predicted to result in massive truncation of the protein. Several new polymorphisms, but no tumor-associated mutations, were found in sporadic tumors.


CONCLUSIONS
Gli3 is mutated rarely in medulloblastoma.
Department of Pediatric Hemato-Oncology and Institute of Hematology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Ayelet
A
Erez
Tsafra
T
Ilan
Ninette
N
Amariglio
Inna
I
Muler
Frida
F
Brok-Simoni
Gideon
G
Rechavi
Shai
S
Izraeli
D002528:Cerebellar Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008527:Medulloblastoma / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3