Article

Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma.

Department of Orthopedics, Otto-von-Guericke University, Magdeburg, Germany.
Pathology - Research and Practice (impact factor: 1.21). 02/2003; 199(6):437-44. pp.437-44
Source: PubMed

ABSTRACT In this case of a dedifferentiated chondrosarcoma, we searched for genetic or epigenetic alterations in both components of the tumor, the low grade chondroblastic component, and the high grade osteosacomatouscomponent. To date, only little is known about aberrant patterns of DNA methylation in chondrosarcomas. Microdissection was used as a valuable method for clearly separating the tissues. We examined CpG island methylation of 8 tumor suppressor genes and candidate tumor suppressor genes, which are involved in different pathways: cell cycle (p21WAF1, p16INK4, p14ARF), apoptosis (DAPK, FHIT), DNA repair (hMLH1), and cell adherence (E-Cadherin). We found p16INK4 and E-cadherin promotor methylation in the low grade chondroid compartment of the dedifferentiated chondrosarcoma. P16INK4, FHIT, and E-cadherin were methylated in the highly malignant osteosarcomatous compartment of the tumor. Earlier investigations of this chondrosarcoma showed p53 mutation and p53-LOH in the anaplastic component. As shown in this case, it was accompanied by Rb-LOH. Early methylation of p16IK4 and E-cadherin in the chondroid compartment could point to the monoclonal origin of demonstrated dedifferentiated chondrosarcoma. Further alterations, as shown in p53, Rb and FHIT, are responsible for the "switch" to a high grade anaplastic sarcoma.

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Keywords

8 tumor suppressor genes
 
aberrant patterns
 
candidate tumor suppressor genes
 
cell adherence
 
cell cycle
 
chondroid compartment
 
CpG island methylation
 
dedifferentiated chondrosarcoma
 
different pathways
 
DNA methylation
 
E-cadherin promotor methylation
 
epigenetic alterations
 
grade anaplastic sarcoma
 
hMLH1
 
low grade chondroblastic component
 
low grade chondroid compartment
 
malignant osteosarcomatous compartment
 
monoclonal origin
 
p53 mutation
 
valuable method