Molecular analysis of the INK4A/INK4A-ARF gene locus in conventional (central) chondrosarcomas and enchondromas: indication of an important gene for tumour progression.

摘要: Loss of heterozygosity (LOH) at chromosomal band 9p21 is one the few consistent genetic aberrations found in conventional chondrosarcoma. This locus harbours two cell-cycle regulators, CDKN2A/p16/INK4A and INK4A-p14ARF, which are inactivated various human malignancies. It was therefore hypothesized that this also plays a role development chondrosarcoma investigated protein, genetic, epigenetic levels. p16 protein expression detected by immunohistochemistry 12 73 central chondrosarcomas it correlated with increasing histological grade (p = 0.001). not 51 enchondromas, presumed to be potential precursors LOH 15 39 (38%) but did correlate loss expression. SSCP analysis reveal any mutations 47 cases. Also, p14 target LOH, since gave no aberrant bands on SSCP. To investigate whether an mechanism operating, methylation-specific PCR used look promotor methylation, identified 5 30 tumours. However, expression, or 9p21. Cytogenetic data were available subset All tumours showed chromosome 9 alterations INK4A/p16 concluded although some DNA level promoter level, lack correlation between indicates other than CDKN2A/p16 must The tumour grade, retention may important event during progression from enchondroma chondrosarcoma, after recurrence Copyright © 2004 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.