Amplification of CDK4 and MDM2 in malignant melanoma Journal Article

Authors: Muthusamy, V.; Hobbs, C.; Nogueira, C.; Cordon-Cardo, C.; McKee, P. H.; Chin, L.; Bosenberg, M. W.
Article Title: Amplification of CDK4 and MDM2 in malignant melanoma
Abstract: 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. © 2006 Wiley-Liss, Inc.
Keywords: osteosarcoma; controlled study; human tissue; glioma; polymerase chain reaction; gene; gene targeting; gene overexpression; melanoma; gene amplification; protein p53; gene mapping; genome analysis; rna, messenger; quantitative analysis; amplicon; gene loss; dna determination; chromosome 12q; liposarcoma; cyclin dependent kinase 4; protein mdm2; proto-oncogene proteins c-mdm2; genes, p53; cyclin-dependent kinase 4; chromosomes, human, pair 12; protein p14arf; protein p16ink4a; cdk4 gene; mdm2 gene; genes, retinoblastoma
Journal Title: Genes Chromosomes and Cancer
Volume: 45
Issue: 5
ISSN: 1045-2257
Publisher: Wiley Periodicals, Inc  
Date Published: 2006-05-01
Start Page: 447
End Page: 454
Language: English
DOI: 10.1002/gcc.20310
PUBMED: 16419059
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 40" - "Export Date: 4 June 2012" - "CODEN: GCCAE" - "Source: Scopus"
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