Somatic Mosaicism in AKT1 Causes Proteus Syndrome

Up to 50 percent of mutant alleles present in mutant cell lines with greater AKT phosphorylation

WEDNESDAY, July 27 (HealthDay News) -- A somatic activating mutation in the oncogene AKT1 has been found to cause Proteus syndrome, a condition characterized by the overgrowth of skin, connective tissue, brain, and other tissues, according to a study published online July 27 in the New England Journal of Medicine.

Marjorie J. Lindhurst, Ph.D., from the National Human Genome Research Institute in Bethesda, Md., and colleagues assessed whether Proteus syndrome is caused by somatic mosaicism for a mutation. DNA sequences from biopsy samples of affected tissues were compared with unaffected tissues. The observed association was confirmed and extended by analyzing the DNA with custom-restriction enzyme assay in 158 samples from 29 patients. The AKT protein activation in affected tissues was assayed by phosphorylation-specific antibodies on Western blots.

The investigators identified a somatic activating mutation in the oncogene AKT1 in 26 of the 29 patients. Admixtures of mutant alleles ranging from 1 to 50 percent were found in the tissues and cell lines from the patients, with mutant cells showing greater AKT phosphorylation than control cell lines. AKT phosphorylation levels differed in a pair of single-cell clones generated from the same starting culture but differing in their mutation status.

"The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism," the authors write.

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