¹Institut für Humangenetik, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany

²Universitätskinderklinik, Universität Ulm, Prittwitzstrae 43, 89075 Ulm, Germany

^aAuthor for correspondence

^bPresent address: Abteilung für Angewandte Physiologie, Universität Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany

Peripheral blood cell DNA from a patient with a chronic myeloproliferative disorder was tested in the tumorigenicity assay. Upon tumor induction in nude mice we isolated a human oncogene by means of genomic cloning, exon trap analysis and cDNA cloning. Sequence analysis revealed a fusion product of the p85 subunit of phosphatidylinositol (PI) 3-kinase and HUMORF8, a putative deubiquitinating enzyme, which has been generated during the DNA transfection process. Application of the tumorigenicity assay to various p85 and HUMORF8 cDNA constructs indicated that the recombination of both genes rather than the truncation of one of the fusion partners renders the chimeric protein tumorigenic. Moreover, sequence analysis of human wildtype p85 revealed an alanine for serine substitution at a site important for the regulation of the lipid kinase activity of PI 3-kinase in human p85. This variation may relate to differences in the mode of signal transduction from both p85 isoforms.

p85; phosphatidylinositol 3-kinase; HUMORF8; deubiquitinating enzyme