The Simpson-Golabi-Behmel gene, GPC3, is not involved in sporadic Wilms tumorigenesis.
Many genes have been implicated in Wilms tumor; however, only one gene, WT1, has a proven role in the development of this embryonal tumor. Wilms tumor occurs in a number of congenital syndromes including the Simpson-Golabi-Behmel syndrome (SGBS) which has phenotypic overlap with another Wilms tumor-predisposing syndrome Wiedemann-Beckwith syndrome. The putative function and expression pattern of the SGBS gene, glypican 3 (GPC3), makes it an attractive candidate Wilms tumor gene. We, therefore, hypothesized that Wilms tumors from non-SGBS patients may harbor somatic mutations of GPC3. Mutation analysis of 64 Wilms tumors was performed. One case of a tumor-specific deletion of the entire GPC3 gene and several polymorphisms were identified. GPC3 expression was evaluated in 36 Wilms tumors and 29/36 expressed GPC3. Surprisingly, we did not find evidence of functional mutations of GPC3 in sporadic Wilms tumor suggesting that GPC3 is not often directly involved in Wilms tumorigenesis.
Gillan
Tanya L
TL
Department of Oncology, University of Alberta, Cross Cancer Institute,11560 University Avenue, Edmonton, Alberta, Canada.
Hughes
Rhiannon
R
Godbout
Roseline
R
Grundy
Paul E
PE
D004252:DNA Mutational Analysis; D015870:Gene Expression; D053673:Glypicans; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
C105937:GPC3 protein, human; D053673:Glypicans; D008565:Membrane Proteins; D009363:Neoplasm Proteins