ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
A somatic activating NRAS variant associated with kaposiform lymphangiomatosis.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07072403 (Safety and Efficacy of Trametinib for Complicated Vascular Anomalies), which is not on this map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety and Efficacy of Trametinib for Complicated Vascular Anomalies: A Multicenter Prospective Study
Who cites it
69 citing papers in PubMed, 134 citations in OpenAlex.
- Trial
- RAS-PI3Kα signaling regulates KrasG12D-induced lymphangiogenesis in complex lymphatic anomalies.Disease models & mechanisms · 2026Article
- RAS Inhibitor RMC-7977 Blocks Vascular Overgrowth of NRASJournal of cellular and molecular medicine · 2026Article
- Sirolimus outperforms alpelisib in models ofBlood vessels, thrombosis & hemostasis · 2026Article
- MEK Inhibition Reduces Vascular Malformations and Gene Dysregulation in NRASPediatric blood & cancer · 2026Article
- Interventional embolization for hemorrhagic pleural effusion in an infant with kaposiform lymphangiomatosis: a case report.Frontiers in medicine · 2026Article
- Long-term low-dose sirolimus therapy and successful discontinuation in an adult with kaposiform lymphangiomatosis and disseminated intravascular coagulation: a case report.Frontiers in medicine · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Resolution of Refractory Chylous Effusions With Targeted MEK Inhibition in NRAS Q61R-Driven Kaposiform Lymphangiomatosis: A Case Report.Case reports in pediatrics · 2026Article
- Trametinib normalizes angiopoietin-2 levels and successfully treats kaposiform lymphangiomatosis.Journal of vascular anomalies · 2025Article
- Human Lymphatic Endothelial Cells Expressing NRASPediatric blood & cancer · 2025Article
- Expansion of the Phenotype of Lymphatic Anomalies Caused by Somatic Activating BRAF Variant.Pediatric blood & cancer · 2025Article
- Zebrafish Models of Induced Lymphangiogenesis: Current Advancements and Therapeutic Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- RAS Pathway Mutations and Therapeutics in Vascular Anomalies.Pediatric blood & cancer · 2025Review
- Targeted Therapies for Slow-Flow Vascular Malformations.The Australasian journal of dermatology · 2025Review
- Lyve1-Driven NrasPediatric blood & cancer · 2025Article
- A single-cell atlas of normal and KRASG12D-malformed lymphatic vessels.JCI insight · 2025Article
- Case Report: Life-threatening Kasabach-Merritt phenomenon in a 2-month-old child.Frontiers in pediatrics · 2025Article
- Hemostasis and thrombosis risks and management in vascular anomalies.Hematology. American Society of Hematology. Education Program · 2024Article
- Targeted medical therapies for vascular anomalies.Hematology. American Society of Hematology. Education Program · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeKaposiform lymphangiomatosis (KLA) is a rare, frequently aggressive, systemic disorder of the lymphatic vasculature, occurring primarily in children. Even with multimodal treatments, KLA has a poor prognosis and high mortality rate secondary to coagulopathy, effusions, and systemic involvement. We hypothesized that, as has recently been found for other vascular anomalies, KLA may be caused by somatic mosaic variants affecting vascular development.
methodsWe performed exome sequencing of tumor samples from five individuals with KLA, along with samples from uninvolved control tissue in three of the five. We used digital polymerase chain reaction (dPCR) to validate the exome findings and to screen KLA samples from six other individuals.
resultsWe identified a somatic activating NRAS variant (c.182 A>G, p.Q61R) in lesional tissue from 10/11 individuals, at levels ranging from 1% to 28%, that was absent from the tested control tissues.
conclusionThe activating NRAS p.Q61R variant is a known "hotspot" variant, frequently identified in several types of human cancer, especially melanoma. KLA, therefore, joins a growing group of vascular malformations and tumors caused by somatic activating variants in the RAS/PI3K/mTOR signaling pathways. This discovery will expand treatment options for these high-risk patients as there is potential for use of targeted RAS pathway inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.