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

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

54 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
Early online date	3 Feb 2018
DOIs	https://doi.org/10.1007/s10456-018-9595-8
State	Published - 1 May 2018
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018, Springer Science+Business Media B.V., part of Springer Nature.

Funding

Acknowledgements We thank M. Grunspan for help with zebrafish experiments; Sarit Farage-Barhom for her help with bioinformatics analysis; Michael Dellinger, The Lymphatic Malformation Institute (LMI) for fruitful discussions. This project was supported by grants from the Israel Science Foundation (Grant No. 1716/11 to S.G.), Basil O’Connor Starter Scholar Research Award Grant from the March of Dimes (No. 5-FY12-55, to S.G), Marie Curie Re-integration grant (FP7-PEOPLE-2010-IRG to S.G). We thank M. Grunspan for help with zebrafish experiments; Sarit Farage-Barhom for her help with bioinformatics analysis; Michael Dellinger, The Lymphatic Malformation Institute (LMI) for fruitful discussions. This project was supported by grants from the Israel Science Foundation (Grant No. 1716/11 to S.G.), Basil O’Connor Starter Scholar Research Award Grant from the March of Dimes (No. 5-FY12-55, to S.G), Marie Curie Re-integration grant (FP7-PEOPLE-2010-IRG to S.G).

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
Israel Science Foundation

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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Somatic NRAS mutation in patient with generalized lymphatic anomaly

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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