Amplification of CDK4 and MDM2 in malignant melanoma.
Amplification of the 12q13-15 region is a common event in several human tumors including liposarcomas, gliomas, and osteosarcomas. We have demonstrated high-level amplification of 12q14 in a subset of uncultured malignant melanomas (3 of 53). High-resolution mapping of the amplicon using quantitative PCR revealed a bipartite amplicon consisting of a primary 50-kb amplicon centered on CDK4 and a secondary amplicon centered on MDM2, without amplification of the intervening 11 Mb of genomic DNA. Analysis of mRNA and protein levels in melanomas with 12q14 amplification demonstrated overexpression of target genes CDK4 and MDM2 without loss of CDKN2A-P16 (P16INK4A) or CDKN2A-P14ARF (P14ARF) expression, important regulators of the RB1 and TP53 pathways, which are commonly lost or mutated in melanoma. These results suggest that coamplification of CDK4 and MDM2 may substitute for loss of P16INK4A and P14ARF function in a subset of melanomas.
Muthusamy
Viswanathan
V
Department of Pathology, University of Vermont, Burlington, Vermont 05495, USA.
Hobbs
Cara
C
Nogueira
Cristina
C
Cordon-Cardo
Carlos
C
McKee
Phillip H
PH
Chin
Lynda
L
Bosenberg
Marcus W
MW
D002881:Chromosomes, Human, Pair 12; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4