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.
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Co-amplification of MDM2 and CDK4 has been reported in several types of cancers including sarcoma, glioblastoma, bladder cancer and gastric cancer.
“Moreover, the co-amplification of MDM2 and CDK4 has been reported in several type of cancers including sarcoma, glioblastoma, bladder cancer, gastric cancer, etc.40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50”
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- Authors
- Muthusamy, V., Hobbs, C., Nogueira, C., Cordon‐Cardo, C., McKee, P. H., Chin, L., & Bosenberg, M. W.
- Affiliations
- University of Vermont (US)
- Universidade do Porto (PT)
- Memorial Sloan Kettering Cancer Center (US)
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Bosenberg, Marcus W.
- Venue
- Genes Chromosomes and Cancer
- Publisher
- Wiley
- Published
- 2006-01-17
- Volume
- 45
- Issue
- 5
- Pages
- 447-454
- ISSN
- 1045-2257 (ISSN-L)
- 1098-2264
- OpenAlex
- W1923073040
- Cited by
- 148
- References
- 22
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 12 · 2013: 19 · 2012: 14
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Chromosomes and Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ulsan National Institute of Science and Technology
- National Cancer Institute (K08 CA89124, P30CA022435, P30-CA 22435, K08CA089124, R01CA112054)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- melanoma, CDK4, MDM2, chromosomal amplification, CDKN2A, p16INK4a, p14ARF, p53 pathway, gene overexpression
- MeSH terms
- Chromosomes, Human, Pair 12, Gene Amplification, Humans, Melanoma, RNA, Messenger, Polymerase Chain Reaction, Genes, p53, Genes, Retinoblastoma, Cyclin-Dependent Kinase 4, Proto-Oncogene Proteins c-mdm2
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