These abnormalities in telomere genes are concurrent with <i>IDH1</i>/<i>IDH2</i> mutation and with <i>CDKN2A/2B</i> deletion or <i>TP53</i> mutation, suggesting a possible association and synergy among these genes in chondrosarcoma progression.
We show that p16/CDKN2A copy number variation occurs subsequent to the IDH1 mutation, and confirm that p16/CDKN2A copy number variation occurs in 75% of high grade central chondrosarcomas, and not in low grade cartilaginous tumours.
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.
Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro.
These results support the hypothesis that p16(ink4a) plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.
These results support the hypothesis that p16(ink4a) plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.
These data suggest that chromosome 9p21 abnormality, and deletions of the CDKN2 and MTS2 tumor suppressor genes may be a significant event in the development of chondrosarcomas.