Recurrent inactivating RASA2 mutations in melanoma

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

doi:10.1038/ng.3427

Recurrent inactivating RASA2 mutations in melanoma

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. RosenbergJaved Khan, Shifra Ben-Dor, Masha Y. Niv, Igor Ulitsky, Graham J. Mann, Richard A. Scolyer, Nicholas K. Hayward, Yardena Samuels

School of Medicine

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1408-1410
Number of pages	3
Journal	Nature genetics
Volume	47
Issue number	12
DOIs	https://doi.org/10.1038/ng.3427
State	Published - Dec 1 2015

ASJC Scopus subject areas

Genetics

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Arafeh, R., Qutob, N., Emmanuel, R., Keren-Paz, A., Madore, J., Elkahloun, A., Wilmott, J. S., Gartner, J. J., Di Pizio, A., Winograd-Katz, S., Sindiri, S., Rotkopf, R., Dutton-Regester, K., Johansson, P., Pritchard, A. L., Waddell, N., Hill, V. K., Lin, J. C., Hevroni, Y., ... Samuels, Y. (2015). Recurrent inactivating RASA2 mutations in melanoma. Nature genetics, 47(12), 1408-1410. https://doi.org/10.1038/ng.3427

Arafeh, R, Qutob, N, Emmanuel, R, Keren-Paz, A, Madore, J, Elkahloun, A, Wilmott, JS, Gartner, JJ, Di Pizio, A, Winograd-Katz, S, Sindiri, S, Rotkopf, R, Dutton-Regester, K, Johansson, P, Pritchard, AL, Waddell, N, Hill, VK, Lin, JC, Hevroni, Y, Rosenberg, SA, Khan, J, Ben-Dor, S, Niv, MY, Ulitsky, I, Mann, GJ, Scolyer, RA, Hayward, NK & Samuels, Y 2015, 'Recurrent inactivating RASA2 mutations in melanoma', Nature genetics, vol. 47, no. 12, pp. 1408-1410. https://doi.org/10.1038/ng.3427

@article{942bac5fe8ec4470a720d57b1b2fd939,

title = "Recurrent inactivating RASA2 mutations in melanoma",

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.",

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

note = "Funding Information: 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{\textquoteright}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. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc. All rights reserved.",

year = "2015",

month = dec,

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doi = "10.1038/ng.3427",

language = "English (US)",

volume = "47",

pages = "1408--1410",

journal = "Nature genetics",

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T1 - Recurrent inactivating RASA2 mutations in melanoma

AU - Arafeh, Rand

AU - Qutob, Nouar

AU - Emmanuel, Rafi

AU - Keren-Paz, Alona

AU - Madore, Jason

AU - Elkahloun, Abdel

AU - Wilmott, James S.

AU - Gartner, Jared J.

AU - Di Pizio, Antonella

AU - Winograd-Katz, Sabina

AU - Sindiri, Sivasish

AU - Rotkopf, Ron

AU - Dutton-Regester, Ken

AU - Johansson, Peter

AU - Pritchard, Antonia L.

AU - Waddell, Nicola

AU - Hill, Victoria K.

AU - Lin, Jimmy C.

AU - Hevroni, Yael

AU - Rosenberg, Steven A.

AU - Khan, Javed

AU - Ben-Dor, Shifra

AU - Niv, Masha Y.

AU - Ulitsky, Igor

AU - Mann, Graham J.

AU - Scolyer, Richard A.

AU - Hayward, Nicholas K.

AU - Samuels, Yardena

N1 - Funding Information: 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. Publisher Copyright: © 2015 Nature America, Inc. All rights reserved.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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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Recurrent inactivating RASA2 mutations in melanoma

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