Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis

Citation
Jvmg. Bovee et al., Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis, J PATHOLOGY, 189(4), 1999, pp. 454-462
Citations number
35
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF PATHOLOGY
ISSN journal
00223417 → ACNP
Volume
189
Issue
4
Year of publication
1999
Pages
454 - 462
Database
ISI
SICI code
0022-3417(199912)189:4<454:MGCOBC>2.0.ZU;2-3
Abstract
Dedifferentiated chondrosarcoma is defined as a high-grade, anaplastic sarc oma adjacent to a low-grade malignant cartilage-forming tumour. Controversy remains as to whether the anaplastic and cartilaginous components are deri ved from a common precursor cell, or whether they represent separate genoty pic lineages (collision tumour). Both components of a case of dedifferentia ted chondrosarcoma mere therefore separately investigated by loss of hetero zygosity (LOH) analysis, comparative genomic hybridization (CGH), DNA how c ytometry, and p53 analysis. Both showed p53 overexpression and an identical somatic 6 bp deletion in exon 7 of p53. Combination of the CGH and LOH res ults revealed that both components had lost the same copy of chromosome 13. These results provide compelling evidence in this case for a common origin , instead of the 'collision tumour' theory. Certain genotypic alterations m ere not shared. The anaplastic component showed severe aneuploidy, LOH at a dditional loci, and amplification and deletion of several chromosome parts. In contrast, the cartilaginous component had lost chromosomes 5, 22, 17p a nd part of 16p and revealed an amplification of 17q. The LOH and CGH result s further demonstrated that the two components had lost a different copy of chromosome 4. Thus, a substantial number of genetic alterations have occur red after the diversion of the two components, indicating that the separati on of the two clones, derived from a single precursor, was a relatively ear ly event in the histogenesis of this case of dedifferentiated chondrosarcom a. Copyright (C) 1999 John Whey & Sons, Ltd.