Recurrent inactivating RASA2 mutations in melanoma.
Rand ArafehNouar QutobRafi EmmanuelAlona Keren-PazJason MadoreAbdel ElkahlounJames S WilmottJared J GartnerAntonella Di PizioSabina Winograd-KatzSivasish SindiriRon RotkopfKen Dutton-RegesterPeter JohanssonAntonia L PritchardNicola WaddellVictoria K HillJimmy C LinYael HevroniSteven A RosenbergJaved KhanShifra Ben-DorMasha Y NivIgor UlitskyGraham J MannRichard A ScolyerNicholas K HaywardYardena SamuelsPublished in: Nature genetics (2015)
Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer.