| The identification of genetic loci of tumor suppressor genes responsible for familial cancer syndromes can be extrapolated to sporadic malignancies such as malignant gliomas.;The CDKN2A gene has many features of a tumor suppressor gene: it maps to 9p21, a region of loss of heterozygozity in a variety of tumor types; it encodes p16;We also have analyzed the CDKN2A gene and p16;Despite this extensive structural and functional evidence, other suppressor genes in the 9p21 region and the large sizes of the deletions has made it difficult to be certain that the CDKN2A gene is their actual target. Thus, we tested this hypothesis by determining the growth suppressive effect, cell cycle inhibition, and the activity of seven naturally occurring glioma-derived CDKN2A alleles carrying point mutations and found that two of them were functionally compromised. To resolve discrepancies among the different existing functional assays, we developed an assay for p16;Taken together, these results suggest the involvement of p16... |
