Decreased expression of the INK4 family of cyclin-dependent kinase inhibitors in Wilms tumor

Cyclin-dependent kinase (CDK) inhibitors represented by the INK4 family (in cluding p16(INK4a), (CDKN2A), p15(INK4b), (CDKN2B) p18(INK4c,CDKN2C), and p 19(INK4d), (CDKN2D)) are regulators of the cell cycle shown to be aberrant in many types of human cancer. We tested the hypothesis that these CDK inhi bitors are a target for altered gene expression in Wilms tumor. Using RT-PC R, gene expression of the INK4 family was found to be decreased in 9 of 38 Wilms tumor samples obtained from the National Wilms Tumor Study Group (NWT SG) tissue bank. All the affected tumor samples were of favorable histology , Methylation-specific PCR revealed that methylation in the p16 promoter re gion may be responsible for altered expression. The incidence of loss of p1 6 expression may increase with increasing tumor stage, i.e., 1/10 (10%) wit h stage I/II FH Wilms tumor, 2/10 (20%) with stage III FH Wilms tumor, and 4/10 (40%) with stage IV FH Wilms tumor. Thus, determining the expression s tatus of the INK4 Family may have potential prognostic value in the managem ent of Wilms tumor. Genes Chromosomes Cancer 29:63-69, 2000. (C) 2000 Wiley -Liss, Inc.