Merck

Recurrent inactivating RASA2 mutations in melanoma.

Nature genetics (2015-10-27)
Rand Arafeh, Nouar Qutob, Rafi Emmanuel, Alona Keren-Paz, Jason Madore, Abdel Elkahloun, James S Wilmott, Jared J Gartner, Antonella Di Pizio, Sabina Winograd-Katz, Sivasish Sindiri, Ron Rotkopf, Ken Dutton-Regester, Peter Johansson, Antonia L Pritchard, Nicola Waddell, Victoria K Hill, Jimmy C Lin, Yael Hevroni, Steven A Rosenberg, Javed Khan, Shifra Ben-Dor, Masha Y Niv, Igor Ulitsky, Graham J Mann, Richard A Scolyer, Nicholas K Hayward, Yardena Samuels
ABSTRACT

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.

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