Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma.
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.
Röpke
M
M
Department of Orthopedics, Otto-von-Guericke University, Magdeburg, Germany. martin.roepke@medizin.uni-magdeburg.de
Boltze
C
C
Neumann
H W
HW
Roessner
A
A
Schneider-Stock
R
R
D015820:Cadherins / Q000235:genetics; D002813:Chondrosarcoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis* / Q000302:isolation & purification; D004210:Dissection / Q000295:instrumentation / Q000379:methods; D005260:Female; D005266:Femoral Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005269:Femur / Q000473:pathology; D050723:Fractures, Bone / Q000209:etiology; D019942:Genes, p16; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics
D015820:Cadherins; D004273:DNA, Neoplasm