LOSS OF IMPRINTING OF THE INSULIN-LIKE-GROWTH-FACTOR-II GENE IN RENAL-CELL-CARCINOMA

Loss of imprinting (LOI) has been implicated in the pathogenesis of em bryonal malignancies as well as adult cancers. Insulin-like growth fac tor II (IGF2) gene is an imprinted gene, normally transcribed only fro m the paternal allele. We investigated allele-specific expression of t he IGF2 gene in 22 cases of renal cell carcinoma (RCC), a common adult -onset renal tumor. Sixteen cases (72%) were informative for IGF2 gene expression, and 9 (56%) of these cases showed biallelic expression of the IGF2 gene. Additionally, in four cases with biallelic expression from which uninvolved kidney tissue was available, LOI of the IGF2 gen e was also demonstrated in the normal tissue. All cases with LOI of IG F2 were low-grade and low-stage tumors. LOI of the IGF2 gene in RCC wa s not associated with overexpression of IGF2 mRNA, whereas IGF2 overex pression was frequently observed in high-stage tumors. These results s uggest that LOI of IGF2 predisposes to low-grade and low-stage tumors, whereas IGF2 overexpression may have a role in RCC tumor progression.