Somatic NRAS mutation in patient with generalized lymphatic anomaly

Eugenia Manevitz-Mendelson; Gil S. Leichner; Ortal Barel; Inbal Davidi-Avrahami; Limor Ziv-Strasser; Eran Eyal; Itai Pessach; Uri Rimon; Aviv Barzilai; Abraham Hirshberg; Keren Chechekes; Ninette Amariglio; Gideon Rechavi; Karina Yaniv; Shoshana Greenberger

doi:10.1007/s10456-018-9595-8

Somatic NRAS mutation in patient with generalized lymphatic anomaly

Eugenia Manevitz-Mendelson, Gil S. Leichner, Ortal Barel, Inbal Davidi-Avrahami, Limor Ziv-Strasser, Eran Eyal, Itai Pessach, Uri Rimon, Aviv Barzilai, Abraham Hirshberg, Keren Chechekes, Ninette Amariglio, Gideon Rechavi, Karina Yaniv, Shoshana Greenberger^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

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.

Original language	English
Pages (from-to)	287-298
Number of pages	12
Journal	Angiogenesis
Volume	21
Issue number	2
DOIs	https://doi.org/10.1007/s10456-018-9595-8
State	Published - 1 May 2018

Funding

Funders	Funder number
Israel Science Foundation	1716/11
March of Dimes
Marie Curie Re-integration	FP7-PEOPLE-2010-IRG
March of Dimes Foundation	5-FY12-55
FP7 People: Marie-Curie Actions	PEOPLE-2010-IR

Keywords

Lymphangiomatosis
Mutation
NRAS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10456-018-9595-8

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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. https://doi.org/10.1007/s10456-018-9595-8

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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.",

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AU - Ziv-Strasser, Limor

AU - Eyal, Eran

AU - Pessach, Itai

AU - Rimon, Uri

AU - Barzilai, Aviv

AU - Hirshberg, Abraham

AU - Chechekes, Keren

AU - Amariglio, Ninette

AU - Rechavi, Gideon

AU - Yaniv, Karina

AU - Greenberger, Shoshana

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AB - 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.

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Somatic NRAS mutation in patient with generalized lymphatic anomaly

Abstract

Funding

Keywords

UN SDGs

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