Decreased expression of the INK4 family of cyclin-dependent kinase inhibitors in Wilms tumor.
Cyclin-dependent kinase (CDK) inhibitors represented by the INK4 family (including p16(INK4a, CDKN2A), p15(INK4b, CDKN2B), p18(INK4c, CDKN2C), and p19(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 inhibitors are a target for altered gene expression in Wilms tumor. Using RT-PCR, 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 (NWTSG) tissue bank. All the affected tumor samples were of favorable histology. Methylation-specific PCR revealed that methylation in the p16 promoter region may be responsible for altered expression. The incidence of loss of p16 expression may increase with increasing tumor stage, i.e., 1/10 (10%) with 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 status of the INK4 family may have potential prognostic value in the management of Wilms tumor.
Department of Oncology, University of Calgary, the Southern Alberta Cancer Research Group, the Alberta Children's Hospital and Tom Baker Cancer Center, Calgary, Alberta, Canada.
M Y
MY
Arcellana-Panlilio
R M
RM
Egeler
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E
Ujack
A
A
Pinto
D J
DJ
Demetrick
S M
SM
Robbins
M J
MJ
Coppes
D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D018797:Cell Cycle Proteins; D002648:Child; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D019942:Genes, p16 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D010865:Pilot Projects; D011379:Prognosis; D025521:Tumor Suppressor Proteins; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism*
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases