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.
Journal article
Recurrent inactivating RASA2 mutations in melanoma
Nature Genetics, Vol.47(12), pp.1408-1410
Dec/2015
Abstract
Details
- Title
- Recurrent inactivating RASA2 mutations in melanoma
- Creators
- Rand Arafeh (null) - 972WIS_INST___122Nouar Qutob (null) - 972WIS_INST___122Rafi Emmanuel (null) - 972WIS_INST___122Alona Keren-Paz (null) - 972WIS_INST___111Jason Madore (null) - University of SydneyAbdel Elkahloun (null) - National Human Genome Research InstituteJames S. Wilmott (null) - University of SydneyJared J. Gartner (null) - National Cancer Institute (United States, Rockville) - NCIAntonella Di Pizio (null) - Hebrew University of JerusalemSabina Winograd-Katz (null) - 972WIS_INST___122Sivasish Sindiri (null) - National Cancer Institute (United States, Rockville) - NCIRon Rotkopf (null) - 972WIS_INST___113Ken Dutton-Regester (null) - QIMR Berghofer Medical Research InstitutePeter Johansson (null) - QIMR Berghofer Medical Research InstituteAntonia L. Pritchard (null) - QIMR Berghofer Medical Research InstituteNicola Waddell (null) - QIMR Berghofer Medical Research InstituteVictoria K. Hill (null) - National Human Genome Research InstituteJimmy C. Lin (null) - National Cancer Institute (United States, Rockville) - NCIYael Hevroni (null) - The Weizmann Institute of ScienceSteven A. Rosenberg (null) - National Cancer Institute (United States, Rockville) - NCIJaved Khan (null) - National Cancer Institute (United States, Rockville) - NCIShifra Ben-Dor (null) - 972WIS_INST___113Masha Y. Niv (null) - Hebrew University of JerusalemIgor Ulitsky (null) - The Weizmann Institute of ScienceGraham J. Mann (null) - University of SydneyRichard A. Scolyer (null) - University of SydneyNicholas K. Hayward (null) - QIMR Berghofer Medical Research InstituteYardena Samuels (Corresponding Author) - 972WIS_INST___122
- Resource Type
- Journal article
- Publication Details
- Nature Genetics, Vol.47(12), pp.1408-1410; Dec/2015
- Number of pages
- 3
- Language
- English
- DOI
- https://doi.org/10.1038/ng.3427
- Grant note
- We thank T. Wiesel for graphical assistance. This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Cancer Institute, as well as by program grants of the Australian National Health and Medical Research Council (NHMRC) and Cancer Institute NSW. Y.S. is supported by the Israel Science Foundation through grants 1604/13 and 877/13, the European Research Council (ERC; StG-335377), the ERC under the European Union's Horizon 2020 research and innovation program (grant agreement 677645), the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics, the estate of Alice Schwarz-Gardos, the estate of John Hunter, the Knell Family, the Peter and Patricia Gruber Award and the Hamburger Family. I.U. is supported by a grant from the Rising Tide Foundation. N.K.H., K.D.-R. and R.A.S. are supported by fellowships from the NHMRC. A.L.P. is supported by Cure Cancer Australia. Support from the Melanoma Institute Australia is also gratefully acknowledged. We thank the TCGA Research Network for generating some of the data sets.
- Record Identifier
- 993264560103596
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