Characterization of the 12q15 MDM2 and 12q13‐14 CDK4 amplicons and clinical correlations in osteosarcoma
Abstract
The chromosomal region 12q13‐15 is recurrently amplified in osteosarcoma (OS), but its importance in bone tumor development remains unknown. Although there are two major candidate genes ( MDM2 , a TP53 downregulator, and CDK4 , involved in cell cycle progression) considered to be the driving genes in this region, the size of the amplicon and number of genes involved have not been determined. In this study, we used 130 classical OS and 15 parosteal OS to determine MDM2 and CDK4 amplification frequency in OS. Tumors in which these genes were amplified were used to map the 12q13‐15 amplified region and to determine its correlation with clinical prognosis. The 12q13‐15 amplification was more prevalent in parosteal OS (67% of cases) than in high‐grade classical OS (12%). Quantitative real‐time PCR of MDM2 , CDK4 , and 25 other genes showed that this region contains two different amplicons: one at 12q15 centered on MDM2 and one at 12q13‐14 centered on CDK4 . Both regions were frequently coamplified in both types of OS, and MDM2 and CDK4 amplification was correlated with higher expression levels for both genes. Univariate and multivariate analyses of clinical data indicated that classical OS patients whose tumors exhibited MDM2 amplification were more likely to be older at diagnosis (median age 32.6 vs. 17.8 years) and female (66.7 vs. 33.3%) than those without gene amplification. There was no association with other clinical parameters. In conclusion, coamplification of MDM2 and CDK4 in two separate amplicons occurs frequently in parosteal OS and less so in classical high‐grade OS. © 2010 Wiley‐Liss, Inc.
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Amplification of MDM genes or altered expression of MDM proteins is a feature of many tumours.
“Amplification of MDM genes or altered expression of MDM proteins is a feature of many tumours3–10 (Table 1).”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [7]
MDM2 and MDMX are deregulated in many human cancers and act oncogenically mainly by inhibiting p53.
“The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [7]
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- Authors
- Mejia‐Guerrero, S., Quejada, M., Gokgoz, N., Gill, M., Parkes, R. K., Wunder, J. S., & Andrulis, I. L.
- Affiliations
- Mount Sinai Hospital (CA)
- Corresponding author
- Andrulis, Irene L.
- Venue
- Genes, Chromosomes and Cancer
- Publisher
- Wiley
- Published
- 2010-03
- Volume
- 49
- Issue
- 6
- Pages
- 518-525
- ISSN
- 1045-2257 (ISSN-L)
- 1098-2264
- OpenAlex
- W1995868292
- Cited by
- 120
- References
- 45
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 3 · 2019: 9 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 12 · 2013: 13 · 2012: 10
- FWCI
- 9.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Chromosomes and Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- osteosarcoma, parosteal osteosarcoma, MDM2, CDK4, co-amplification, cell cycle progression, clinical prognosis, gene expression, age at diagnosis, sex distribution
- MeSH terms
- Adult, Aged, Bone Neoplasms, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 12, Female, Gene Amplification, Humans, Male, Middle Aged, Mutation, Prognosis, Osteosarcoma, Gene Expression, Genes, p53, Cyclin-Dependent Kinase 4, Proto-Oncogene Proteins c-mdm2, Kaplan-Meier Estimate, Young Adult
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