Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/56781
Title: Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly.
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Issue Date: 27-Dec-2018
Citation: J Exp Med.2019;(216)2:407-418
Abstract: Generalized lymphatic anomaly (GLA) is a vascular disorder characterized by diffuse or multifocal lymphatic malformations (LMs). The etiology of GLA is poorly understood. We identified four distinct somatic PIK3CA variants (Glu542Lys, Gln546Lys, His1047Arg, and His1047Leu) in tissue samples from five out of nine patients with GLA. These same PIK3CA variants occur in PIK3CA-related overgrowth spectrum and cause hyperactivation of the PI3K-AKT-mTOR pathway. We found that the mTOR inhibitor, rapamycin, prevented lymphatic hyperplasia and dysfunction in mice that expressed an active form of PIK3CA (His1047Arg) in their lymphatics. We also found that rapamycin reduced pain in patients with GLA. In conclusion, we report that somatic activating PIK3CA mutations can cause GLA, and we provide preclinical and clinical evidence to support the use of rapamycin for the treatment of this disabling and deadly disease.
PMID: 30591517
URI: https://hdl.handle.net/20.500.12530/56781
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > FIB H. Infantil U. Niño Jesús > Artículos

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