FLT4
Overview
FLT4 (also known as VEGFR3) encodes vascular endothelial growth factor receptor 3, a receptor tyrosine kinase involved in VEGF/VEGFR signaling and the stress-activated MAPK cascade. FLT4 is predominantly amplified in radiation-associated angiosarcoma and is enriched compared to sporadic angiosarcoma.
Alterations observed in the corpus
- Mostly amplification in 16% of RT-ANGS vs 8% of sporadic AS; implicated in stress-activated MAPK cascade and VEGF/VEGFR signaling PMID:37350195.
- Co-occurs with MYC amplification, CRKL, HRAS, and KMT2D alterations in breast/chest wall RT-AS PMID:37350195.
- Identified among significantly mutated genes in 188 primary LUAD tumours (TSP cohort); VEGFR-3 receptor tyrosine kinase. PMID:18948947
- FLT4 (VEGFR3) mutations are among the low-frequency RTK hits identified in advanced thyroid cancers (PDTC/ATC) by MSK-IMPACT 341-gene sequencing (n=117 tumors) PMID:26878173
- Identified as a novel recurrently mutated gene (1–4% frequency) in microsatellite-stable metastatic colorectal cancer by MSK-IMPACT sequencing of 1,134 colorectal adenocarcinomas PMID:29316426
Cancer types (linked)
- ANGS — FLT4 amplification enriched in RT-AS (16%) vs sporadic AS (8%); participates in both VEGF/VEGFR signaling and stress-activated MAPK cascade pathways PMID:37350195.
Co-occurrence and mutual exclusivity
- Co-occurs with MYC amplification, CRKL amplification, HRAS hotspot mutations, and KMT2D alterations in RT-AS PMID:37350195.
Therapeutic relevance
- FLT4 is part of both the stress-activated MAPK cascade and VEGF/VEGFR signaling pathways identified as potential molecular targets in RT-AS PMID:37350195.
Open questions
- Whether anti-VEGFR therapy (e.g., pazopanib, bevacizumab) is effective specifically in FLT4-amplified RT-AS is not established PMID:37350195.
Sources
This page was processed by crosslinker on 2026-05-05. - PMID:18948947
This page was processed by crosslinker on 2026-05-05. - PMID:26878173
This page was processed by wiki-cli on 2026-05-14. - PMID:29316426
This page was processed by wiki-cli on 2026-05-15.