Somatic NRAS mutation in patient with generalized lymphatic anomaly

被引：66

作者：

Manevitz-Mendelson, Eugenia ^{[1
]}

Leichner, Gil S. ^{[1
]}

Barel, Ortal ^{[3
]}

Davidi-Avrahami, Inbal ^{[4
]}

Ziv-Strasser, Limor ^{[3
]}

Eyal, Eran ^{[3
]}

Pessach, Itai ^{[2
,5
]}

Rimon, Uri ^{[6
]}

Barzilai, Aviv ^{[1
,2
]}

Hirshberg, Abraham ^{[7
]}

Chechekes, Keren ^{[3
]}

Amariglio, Ninette ^{[2
,3
]}

Rechavi, Gideon ^{[2
,3
]}

Yaniv, Karina ^{[4
]}

Greenberger, Shoshana ^{[1
,2
]}

机构：

[1] Sheba Med Ctr, Dept Dermatol, Ramat Gan, Israel

[2] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[3] Sheba Med Ctr, Sheba Canc Res Ctr, Ramat Gan, Israel

[4] Weizmann Inst Sci, Dept Regulat Biol, Rehovot, Israel

[5] Safra Childrens Hosp, Dept Pediat Crit Care, Sheba Med Ctr, Ramat Gan, Israel

[6] Sheba Med Ctr, Dept Radiol, Ramat Gan, Israel

[7] Tel Aviv Univ, Sch Dent Med, Dept Oral Pathol & Oral Med, Tel Aviv, Israel

来源：

ANGIOGENESIS | 2018年 / 21卷 / 02期

基金：

以色列科学基金会;

关键词：

Lymphangiomatosis; NRAS; Mutation; DIFFUSE PULMONARY LYMPHANGIOMATOSIS; INFANTILE HEMANGIOMA; STEM-CELLS; VASCULAR ANOMALIES; ABNORMALITIES; SIROLIMUS; MELANOMA; CHILD; CLASSIFICATION; BEVACIZUMAB;

D O I：

10.1007/s10456-018-9595-8

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

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.

引用

页码：287 / 298

页数：12

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