Deregulation of the G1/S checkpoint is a frequent event in the development
of glioblastoma multiforme (GBM). Previous studies have shown more than 50%
of primary GEM tumours contain either complete loss of the p16(INK4a) locu
s or amplification of the CDK4 gene. Moreover, many heterozygosity studies
have shown deletion on human chromosome 19p13.2, where the p19(INK4d) gene
has been localized. We examined the expression of p19(INK4d) and its two CD
K substrates in a series of glioma-derived cell lines and tumours. No gene
rearrangement or deletion was observed in the p19(INK4d) gene in these cell
lines; however, expression of CDK4 and CDK6 was elevated relative to match
ed normal brain tissue in eight of 18 GBM tumours (44%). Furthermore, CDK6
expression level was increased in 12/14 glioblastomas, but undetectable in
tumour samples of a previous lower grade tumour from the same patient. Thes
e data attest to the functional importance of both CDK4 and CDK6 in astrocy
tic tumourigenesis, particularly during the later stages of tumour progress
ion.