PUBLICATION
Somatic NRAS mutation in patient with generalized lymphatic anomaly
- Authors
- Manevitz-Mendelson, E., Leichner, G.S., Barel, O., Davidi-Avrahami, I., Ziv-Strasser, L., Eyal, E., Pessach, I., Rimon, U., Barzilai, A., Hirshberg, A., Chechekes, K., Amariglio, N., Rechavi, G., Yaniv, K., Greenberger, S.
- ID
- ZDB-PUB-180206-7
- Date
- 2018
- Source
- Angiogenesis 21(2): 287-298 (Journal)
- Registered Authors
- Yaniv, Karina, Ziv, Limor
- Keywords
- Lymphangiomatosis, Mutation, NRAS
- MeSH Terms
-
- Animals
- Endothelial Cells*
- Extracellular Signal-Regulated MAP Kinases/genetics
- Extracellular Signal-Regulated MAP Kinases/metabolism
- GTP Phosphohydrolases*/genetics
- GTP Phosphohydrolases*/metabolism
- Human Umbilical Vein Endothelial Cells
- Humans
- Lymphatic Vessels/abnormalities
- Lymphatic Vessels/metabolism
- Lymphatic Vessels/pathology
- Membrane Proteins*/genetics
- Membrane Proteins*/metabolism
- Mice
- Mice, SCID
- Mutation*
- TOR Serine-Threonine Kinases/genetics
- TOR Serine-Threonine Kinases/metabolism
- Zebrafish
- PubMed
- 29397482 Full text @ Angiogenesis
Citation
Manevitz-Mendelson, E., Leichner, G.S., Barel, O., Davidi-Avrahami, I., Ziv-Strasser, L., Eyal, E., Pessach, I., Rimon, U., Barzilai, A., Hirshberg, A., Chechekes, K., Amariglio, N., Rechavi, G., Yaniv, K., Greenberger, S. (2018) Somatic NRAS mutation in patient with generalized lymphatic anomaly. Angiogenesis. 21(2):287-298.
Abstract
Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping