Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.
OBJECTIVE
Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification.


METHODS
The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were obtained in a subset of the tumors.


RESULTS
Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Several apparently distinctive aberrations affecting conventional central and peripheral tumors, respectively, were identified. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1, and EXT2 genes. The chromosomal imbalances in two distinct groups of predominantly near-haploid and near-triploid tumors, respectively, support the notion that polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of chondrosarcoma progression. Increasing patient age as well as tumor grade were associated with adverse outcome, but no copy number imbalance affected metastasis development or tumor-associated death.


CONCLUSIONS
Despite similarities in the overall genomic patterns, the present findings suggest that some regions are specifically altered in conventional central and peripheral tumors, respectively.
Hallor
Karolin H
KH
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Staaf
Johan
J
Bovée
Judith V M G
JV
Hogendoorn
Pancras C W
PC
Cleton-Jansen
Anne-Marie
AM
Knuutila
Sakari
S
Savola
Suvi
S
Niini
Tarja
T
Brosjö
Otte
O
Bauer
Henrik C F
HC
Vult von Steyern
Fredrik
F
Jonsson
Kjell
K
Skorpil
Mikael
M
Mandahl
Nils
N
Mertens
Fredrik
F