𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Characterization of the 12q15 MDM2 and 12q13-14 CDK4 amplicons and clinical correlations in osteosarcoma

✍ Scribed by Salvador Mejia-Guerrero; Michael Quejada; Nalan Gokgoz; Mona Gill; Robert K. Parkes; Jay S. Wunder; Irene L. Andrulis

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
456 KB
Volume
49
Category
Article
ISSN
1045-2257

No coin nor oath required. For personal study only.

✦ Synopsis

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.

📜 SIMILAR VOLUMES

Molecular abnormalities in liposarcoma:
Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing amplicons at 12q13-22
✍ Pilotti, Silvana; Della Torre, Gabriella; Lavarino, Cinzia; Sozzi, Gabriella; Mi 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 105 KB

It has recently been shown that mdm2 overexpression with stabilization of p53 represents a characteristic of retroperitoneal well-differentiated-dedifferentiated, here renamed evolved (WD-E), liposarcomas at the immunocytochemical, molecular, and cytogenetic level. This make-up appears to be confine

CDK4 gene amplification in osteosarcoma:
CDK4 gene amplification in osteosarcoma: Reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons
✍ Guo Wei; Fulvio Lonardo; Takafumi Ueda; Tonia Kim; Andrew G. Huvos; John H. Heal 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 French ⚖ 186 KB

The INK4A gene, localized to human chromosome 9p21, encodes p16 INK4A , a tumor suppressor that functions at least in part through the inhibition of CDK4, a cyclin-dependent kinase encoded by a gene at 12q13. To examine INK4A gene alterations in uncultured samples of osteosarcoma and the relationshi

Genomic and clinical analyses of 2p24 an
Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: A report from the Children's Oncology Group
✍ Frederic G. Barr; Fenghai Duan; Lynette M. Smith; Donna Gustafson; Mandy Pitts; 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 519 KB

## Abstract Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer that is related to the skeletal muscle lineage and characterized by recurrent chromosomal translocations. Within the ARMS category, there is clinical and genetic heterogeneity, consistent with the premise that “primary”

Rearrangement of the COL12A1 and COL4A5
Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular cytogenetic delineation of the tumor-specific translocationt(X;6)(q13-14;q22)
✍ Clelia Tiziana Storlazzi; Agnieszka Wozniak; Ioannis Panagopoulos; Raf Sciot; Ni 📂 Article 📅 2005 🏛 John Wiley and Sons 🌐 French ⚖ 523 KB

## Abstract Subungual exostosis is a benign bone‐ and cartilage‐producing tumor occurring in the hands and feet of children and young adults. The recent identification of a recurrent chromosomal translocation t(X;6)(q24‐q26;q15‐21) in short‐term‐cultured tumor cells strongly suggests that subungual

High-resolution genomic analysis of the
High-resolution genomic analysis of the 11q13 amplicon in breast cancers identifies synergy with 8p12 amplification, involving the mTOR targets S6K2 and 4EBP1
✍ Elin Karlsson; Marie Ahnström Waltersson; Josefine Bostner; Gizeh Pérez-Tenorio; 📂 Article 📅 2011 🏛 John Wiley and Sons 🌐 English ⚖ 604 KB

## Abstract The chromosomal region 11q13 is amplified in 15–20% of breast cancers; an event not only associated with estrogen receptor (ER) expression but also implicated in resistance to endocrine therapy. Coamplifications of the 11q13 and 8p12 regions are common, suggesting synergy between the am