Model Cell Lines With and Without AKT1 Mutations Derived from Proteus Syndrome Patients

The Proteus syndrome is a congenital disorder characterized by patchy overgrowth and hyperplasia (cell proliferation) of multiple tissues and organs, along with susceptibility to developing tumors. It is a rare disorder, with incidence of less than one case per million, caused by a somatic mutation. It is also a mosaic disorder, that is one in which cells of the same person have different genetic content from one another. The NHGRI inventors have generated cell lines from patients with Proteus syndrome and discovered that a somatic activating mutation in the serine-threonine kinase AKT1 is associated with Proteus syndrome. AKT1 is an oncogene and an enzyme known to mediate cell proliferation and apoptosis (programmed cell death process) and has been a target for anti-cancer therapies. A number of single-cell lines with the AKT1 mutation showing increased AKT1 phosphorylation and their matched controls without the mutation have been generated. The cell lines can be used to screen therapeutic targets for AKT1, for study design, as models of Proteus syndrome and early stages of cancerous conditions.