Analysis of the p300/CBP-Associated Factor (PCAF) gene in astrocytic tumors

The PCAF gene encodes the p300/CBP-Associated Factor (PCAF), a histone acet yltransferase, which regulates p53 by acetylation of Lys320 in the C-termin al portion of p53. While the p53 gene is one of the most frequently mutated tumor suppressor genes in human tumors, such mutations occur in only 30% o f astrocytic tumors. Since PCAF can regulate p53 activity, abrogation of PC AF function by PCAF gene mutation could be an alternate mechanism to inacti vate the p53 pathway in tumors lacking p53 mutations. To test this hypothes is, we determined the nucleotide sequence of the entire PCAF coding region in 37 astrocytic tumors (17 glioblastomas, 10 anaplastic astrocytomas, 7 lo w-grade astrocytomas, and 3 pilocytic astrocytomas). We detected two single -nucleotide alterations that represented non-deleterious polymorphisms (GAG > GAA Glu103Glu, AAT > AGT Asn386Ser) but no obvious functional mutations. Moreover, the frequency of the Asn386Ser allele that contained Ser386 in g lioma patients was not statistically different from its frequency in indivi duals without disease, and no significant association was observed between the PCAF polymorphisms and the presence or absence of p53 mutations in the tumors. We conclude that the PCAF gene is not mutated during the developmen t of the astrocytic tumors studied here.