VAV1
Overview
VAV1 (Vav Guanine Nucleotide Exchange Factor 1) is a RhoGEF that activates Rac/Rho GTPases and functions as an upstream activator of Ras/Raf/RTK signaling. In lung adenocarcinoma, VAV1 mutations are part of an expanded set of Ras/Raf/RTK pathway drivers that raises the fraction of actionable lung ADC cases to 76–85%, particularly in tumors lacking classical EGFR/ALK/ROS1 drivers.
Alterations observed in the corpus
- Recurrent mutation identified as an expanded RAS-pathway driver in lung adenocarcinoma; inclusion of VAV1 (alongside SOS1, RASA1, ARHGAP35) raises the proportion of lung ADCs with a candidate Ras/Raf/RTK pathway driver to 76% overall in the TCGA Pan-Lung study (1,144 NSCLC cases) PMID:27158780.
Cancer types (linked)
- LUAD: VAV1 mutations expand the druggable RAS-pathway pool in oncogene-negative lung adenocarcinoma; 85% of expert-reviewed lung ADC subset had a candidate Ras/Raf/RTK driver when VAV1 and related genes were included PMID:27158780.
Co-occurrence and mutual exclusivity
- No specific co-occurrence or mutual exclusivity data reported in the current corpus.
Therapeutic relevance
- Inclusion of VAV1 mutations in the Ras/Raf/RTK-pathway driver pool narrows the fraction of lung ADC patients without a candidate targeted therapy; downstream effectors of VAV1-Rac/Rho signaling may represent therapeutic targets PMID:27158780.
Open questions
- The specific functional impact of observed VAV1 mutations in lung ADC, and whether they activate Ras signaling in a manner analogous to RAS hotspot mutations, requires experimental validation.
Sources
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