p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade

The p53 gene is normally wild type in meningiomas. Since all three members of the p53 gene family recognize the same DNA sequence, tumors containing w ild type p53 could decrease transactivation of p53 target genes by mutating either p63 or p73. In meningiomas the most likely target is p73, because l oss of heterozygosity of the chromosomal band containing p73 is the commone st genetic lesion in these tumors. To screen p73 for mutations we have deve loped a functional assay which tests the ability of p73 to activate transcr iption from a p53-responsive promoter in yeast. The assay correctly identif ied p73 mutants with mutations equivalent to hotspot mutations in p53, demo nstrating that the assay can detect transcriptionally inactive p73. No muta tions in p73 were identified in meningiomas. p73 RNA level was higher in mo re advanced tumors, but there was no correlation between the expression lev el of p73 and p21, a known p53 target gene. The yeast assay was also used t o measure the intrinsic sensitivity of the p73 protein to mutagenesis. Like p53, p73 is exceptionally easy to inactivate as a transcription factor by point mutation. Taken together, these results indicate that p53 and p73 ser ve very different functions in tumors.