Identification of a functional mutation in pp32r1 (ANP32C).

No mutations or polymorphisms have previously been reported in pp32r1 (ANP32C; GenBank: AF008216.1). pp32r1 is part of the highly conserved ANP32 family, some of whose members are associated with control of histone acetylation, mRNA stability, and specialized forms of apoptosis. Although 87.6% identical at the protein level, pp32r1 is functionally distinct from pp32 (ANP32A) in its failure to suppress oncogenesis in in vitro transformation systems and its tumorigenicity in in vivo assays. The present study found that pp32r1 expression levels vary among human tumor cell lines, with the highest levels found in prostatic adenocarcinoma cell lines. pp32r1 also appears to be polymorphic at nucleotide g.4520 and nucleotide g.4664 in human tobacco-associated oral mucosal lesions, human fibroblast cell lines, and several carcinoma cell lines. PC-3 human prostatic adenocarcinoma cells likewise appear to be polymorphic at these loci, but additionally contain a g.4870T>C transversion mutation. The mutation results in a p.Tyr140His substitution, which lies in a functionally important region of the molecule. In the PC-3 prostate cancer line, the mutation is either homozygous, or hemizygous accompanied by loss of heterozygosity. ACHN cells stably transfected with pp32r1 containing this mutation showed a markedly increased rate of growth. The pp32r1 mutation could thus be causally associated with the neoplastic growth properties of PC-3, and be of potential clinical significance. Copyright 2004 Wiley-Liss, Inc.