Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly
| العنوان: | Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly |
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| المؤلفون: | Elena Vallespín, Gloria Oliva-Molina, Ana Bustamante, Victor Martinez-Glez, Michael T. Dellinger, Isabel Colmenero, Rebeca Rodríguez Pena, Kristina Ibáñez, Carmen Ayuso, Cristina Villaverde, Noelia Agra, Rubén Martín-Arenas, Devon Hominick, Noor Khurana, Lara Rodriguez-Laguna, Pablo Lapunzina, María J. Beato, Juan Carlos López-Gutiérrez, Angela del Pozo, Gema Gordo, Gonzalo Herranz, Juan M. Torres Canizalez |
| المصدر: | Journal of Experimental Medicine. 216:407-418 |
| بيانات النشر: | Rockefeller University Press, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Mutation, business.industry, Somatic cell, Immunology, nutritional and metabolic diseases, Disease, Hyperplasia, medicine.disease_cause, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Lymphatic system, Vascular Disorder, Etiology, Cancer research, Immunology and Allergy, Medicine, Missense mutation, lipids (amino acids, peptides, and proteins), business, neoplasms, 030215 immunology |
| الوصف: | 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. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::94f598cddd6cb5a6a3b7b7bb97372c89Test https://doi.org/10.1084/jem.20181353Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........94f598cddd6cb5a6a3b7b7bb97372c89 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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