Loss of function mutations in <i>GPC3</i> lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC3-expressing cancers including hepatoblastoma and Wilms tumor.
Glypican-3 mRNA expression by real-time PCR on tumor and normal germline samples from 75 fresh nephrectomies for Wilms tumor with fold change after normalization against GAPDH was compared.
Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies such as Wilms tumor.
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.
Increased expression of GPC3 in Wilms tumor and hepatoblastoma suggests a growth-promoting or neutral activity for this gene product rather than a growth-suppressive effect.
GPC3 was not expressed in normal kidney tissues obtained from the corresponding Wilms' tumor patients, suggesting that in these cancer cells expression was not repressed (or was activated).
Furthermore, our finding of a GPC3 normal daughter of an SGBS carrier with skeletal abnormalities and Wilms tumour raises the possibility of a trans effect from the maternal carrier in SGBS kindreds.
In human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric adenocarcinomas but not in several other types of cancer and 21 nonhepatocellular human tumor cell lines examined.