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Dermatol Clin. 2017 Jan;35(1):51-60. doi: 10.1016/j.det.2016.07.001.

Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway.

Author information

1
Department of Dermatology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
2
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, Building 49, Room 4A56, 49 Convent Drive, National Institutes of Health, Bethesda, MD 20892, USA.
3
Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Building 10, Room 6D05, 10 Center Drive, National Institutes of Health, Bethesda, MD 20892-1590, USA.
4
Department of Dermatology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: thomas.darling@usuhs.edu.

Abstract

Somatic mutations in genes of the PI3K/PTEN/AKT/TSC/mTORC1 signaling pathway cause segmental overgrowth, hamartomas, and malignant tumors. Mosaicism for activating mutations in AKT1 or PIK3CA cause Proteus syndrome and PIK3CA-Related Overgrowth Spectrum, respectively. Postzygotic mutations in PTEN or TSC1/TSC2 cause mosaic forms of PTEN hamartoma tumor syndrome or tuberous sclerosis complex, respectively. Distinct features observed in these mosaic conditions in part reflect differences in embryological timing or tissue type harboring the mutant cells. Deep sequencing of affected tissue is useful for diagnosis. Drugs targeting mTORC1 or other points along this signaling pathway are in clinical trials to treat these disorders.

KEYWORDS:

Mosaicism; Next-generation sequencing; PIK3CA-related overgrowth spectrum; PTEN hamartoma tumor syndrome; Proteus syndrome; Sirolimus; Tuberous sclerosis complex; mTORC1

PMID:
27890237
PMCID:
PMC5130114
DOI:
10.1016/j.det.2016.07.001
[Indexed for MEDLINE]
Free PMC Article

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