Cited by 150Cancer-related Molecular PathwaysCutaneous Melanoma Detection and ManagementMelanoma and MAPK Pathways

Amplification of CDK4 and MDM2 in malignant melanoma

Muthusamy, Viswanathan, Hobbs, Cara, Nogueira, Cristina, Cordon‐Cardo, Carlos, McKee, Phillip H., Chin, Lynda, Bosenberg, Marcus W.·2006·Genes Chromosomes and Cancer

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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Crossref · 10.1002/gcc.20310

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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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