Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function

Mutations of PTEN, which encodes a protein-tyrosine and lipid phosphatase, are prevalent in a variety of human cancers. The human genome 'draft' seque nce still lacks organization and much of the PTEN and adjacent loci remain undefined. The pufferfish, Fugu rubripes, by virtue of having a compact gen ome represents an excellent template for rapid vertebrate gene discovery. S equencing of 56 kb from the Fugu pten (fpten) locus identified four complet e genes and one partial gene homologous to human genes. Genes neighboring f pten include a PAPS synthase (fpapss2) differentially expressed between non -metastatic/metastatic human carcinoma cell lines, an inositol phosphatase (fminpp1) and an omega class glutathione-S-transferase (fgsto). We have det ermined the order of human BAC clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes oriented as are their Fugu orthologs. A lthough the human genes span 500 kb, the Fugu genes lie within only 22 kb d ue to the compressed intronic and intergenic regions that typify this genom e. Interestingly, and providing striking evidence of regulatory element con servation between widely divergent vertebrate species, the compact 2.1 kb f pten promoter is active in human cells. Also, like hPTEN, fpten has a growt h and tumor suppressor activity in human glioblastoma cells, demonstrating conservation of protein function.