The CDKN2A/CDKN2B/CDK4/CCND1 pathway is pivotal in well-differentiated and dedifferentiated liposarcoma oncogenesis. An analysis of 104 tumors

The MDM2 and CDK4 genes are the main targets of chromosome 12 amplification in well‐differentiated and dedifferentiated liposarcomas. Nevertheless, around 10% of these tumors do not amplify CDK4. To find substitutive alterations of CDK4 amplification, we analyzed a large series of liposarcomas by ar...

Full description

Saved in:
Bibliographic Details
Published in:Genes chromosomes & cancer 2011-11, Vol.50 (11), p.896-907
Main Authors: Louis-Brennetot, Caroline, Coindre, Jean-Michel, Ferreira, Céline, Pérot, Gaëlle, Terrier, Philippe, Aurias, Alain
Format: Article
Language:English
Subjects:
Blotting, Western
Cell cycle
Cell Differentiation - physiology
Chromosome 1
Chromosome 12
Comparative Genomic Hybridization
Cyclin D1 - genetics
Cyclin D1 - metabolism
Cyclin-dependent kinase 4
Cyclin-Dependent Kinase 4 - genetics
Cyclin-Dependent Kinase 4 - metabolism
Cyclin-Dependent Kinase Inhibitor p15 - genetics
Cyclin-Dependent Kinase Inhibitor p15 - metabolism
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Differentiation
Female
Gene Amplification
Gene Expression Profiling
Genetic Loci
genomics
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Liposarcoma
Liposarcoma - genetics
Liposarcoma - metabolism
Liposarcoma - pathology
Male
MDM2 protein
Polymerase chain reaction
Real-Time Polymerase Chain Reaction
Signal Transduction
Tumorigenesis
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The MDM2 and CDK4 genes are the main targets of chromosome 12 amplification in well‐differentiated and dedifferentiated liposarcomas. Nevertheless, around 10% of these tumors do not amplify CDK4. To find substitutive alterations of CDK4 amplification, we analyzed a large series of liposarcomas by array‐CGH, real‐time genomic PCR, gene expression array, and real‐time RT‐PCR. We demonstrate that an alteration in the CDKN2A/CDKN2B/CDK4/CCND1 pathway is present in almost all cases without CDK4 amplification, thereby confirming the pivotal role of this pathway in liposarcoma oncogenesis. Moreover, we show that cell cycle and differentiation are driven by a subtle and complex balance between members of this pathway. Finally, we demonstrate that in tumors without amplification/overexpression of CDK4, the chromosome 1q21‐1q23 region is a preferential partner of chromosome 12 amplicon, suggesting that the mechanism of amplification is slightly different in this group of tumors. © 2011 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
1098-2264
DOI:10.1002/gcc.20909