Genetic and genetic expression analyses of clear cell sarcoma of the kidney

Clear cell sarcoma of the kidney (CCSK) represents a significant diagnostic and clinical challenge. In search of diagnostically useful or biologically significant genetic abnormalities, we screened 30 CCSKs from the National Wilms Tumor Study Group. Genetic gains and losses were analyzed using comparative genomic hybridization; loss of heterozygosity at 11p15 was studied using microsatellite analysis. Loss of imprinting (LOI) was studied using allele-specific expression or methylation analysis at the Apal polymorphic site for IGF2, Alul and Rsal sites for H19, and Cfo/site for SNRPN. Comparative genomic hybridization analysis revealed quantitative abnormalities in only 4 of 30 CCSKs. Two showed gain of 1q, one also showed loss of 10q, and the other also showed loss of terminal 4p. The other two cases demonstrated chromosome 19 loss and chromosome 19p gain, respectively. All 22 cases informative for 11 p15 showed retention of both alleles. Of 14 CCSKs informative for IGF2, six showed biallelic expression; all three CCSKs informative for H19 exhibited monoallelic expression. The normal imprint pattern was present in all six CCSKs analyzed for SNRPN methylation. These data demonstrate an absence of consistent genetic gains or losses in CCSKs using these methods. The high frequency of LOI for IGF2 in CCSKs (43%) is comparable to that reported in Wilms tumors. The retention of imprinting at the SNRPN and H19 loci confirm that LOI is not a ubiquitous epigenetic change. This suggests that IGF2, a potent growth factor, may play a role in the development or progression of CCSK.