A novel variant of VEGFR2 identified by a pan-cancer screening of recurrent somatic mutations in the catalytic domain of tyrosine kinase receptors enhances tumor growth and metastasis

In cancer genomics, recurrence of mutations in gene families that share homologous domains has recently emerged as a reliable indicator functional impact and can be exploited to reveal the pro-oncogenic effect previously uncharacterized variants. Pan-cancer analyses mutation hotspots catalytic domain subset tyrosine kinase receptors revealed two infrequent VEGFR2 (R1051Q D1052N) recur analogous proteins correlate with reduced patient survival. Functional validation showed both R1051Q D1052N increase enzymatic activity VEGFR2. The expression VEGFR2R1051Q potentiates PI3K/Akt signaling axis cells, increasing their tumorigenic potential vitro vivo. addition, it confers cells an increased sensitivity VEGFR2-targeted inhibitor Linifanib. context efficacious application anti-cancer targeted therapies, these findings indicate screening for mutations, like VEGFR2R1051Q, may help predict prognosis drug response, significant clinical implications.