Jvmg. Bovee et al., Near-haploidy and subsequent polyploidization characterize the progressionof peripheral chondrosarcoma, AM J PATH, 157(5), 2000, pp. 1587-1595
Citations number
75
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Chondrosarcomas are malignant cartilaginous tumors arising centrally in bon
e (central chondrosarcoma), or secondarily within the cartilaginous cap of
osteochondroma (peripheral chondrosarcoma). We previously used DNA flow cyt
ometry to demonstrate that near-haploidy is relatively frequent In peripher
al chondrosarcomas, We performed fluorescence in situ hybridization (FISH)
to interphase nuclei using centromeric probes, a genome wide loss of hetero
zygosity (LOH) analysis, and comparative genomic hybridization on five peri
pheral chondrosarcomas, We demonstrated near-haploidy in two low-grade tumo
rs with only one copy and LOH of most chromosomes, Pew chromosomes are diso
mic, with retention of heterozygosity and overrepresentation at comparative
genomic hybridization. One tumor contains both a near-haploid clone with c
hromosomes in monosomic and disomic state, and an exactly duplicated clone.
Two high-grade tumors clearly demonstrate polyploidization because most ch
romosomes show LOH and two copies at FISH, whereas few chromosomes have fou
r copies with retention of heterozygosity, Using DNA from a relative, we de
monstrate that chromosome loss Is random regardless of parental origin. Usi
ng FISH on paraffin slides, we exclude near-haploidy to result from meiosis
-like division in binucleated cells, characteristic for chondrosarcoma. In
conclusion, our results indicate that near-haploidy characterizes the progr
ession from osteochondroma toward low-grade chondrosarcoma Moreover, furthe
r progression toward high-grade chondrosarcoma Is characterized by polyploi
dization.