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 (First Author)
, Nouar Qutob (Co-Author)
, Rafi Emmanuel (Co-Author)
, Alona Keren-Paz (Co-Author)
, Jason Madore (Co-Author)
, Abdel Elkahloun (Co-Author)
, James S. Wilmott (Co-Author)
, Jared J. Gartner (Co-Author)
, Antonella Di Pizio (Co-Author)
, Sabina Winograd-Katz (Co-Author)
, Sivasish Sindiri (Co-Author)
, Ron Rotkopf (Co-Author)
, Ken Dutton-Regester (Co-Author)
, Peter Johansson (Co-Author)
, Antonia L. Pritchard (Co-Author)
, Nicola Waddell (Co-Author)
, Victoria K. Hill (Co-Author)
, Jimmy C. Lin (Co-Author)
, Yael Hevroni (Co-Author)
, Steven A. Rosenberg (Co-Author)

Javed Khan (Co-Author), Shifra Ben-Dor (Co-Author), Masha Y. Niv (Co-Author), Igor Ulitsky (Co-Author), Graham J. Mann (Co-Author), Richard A. Scolyer (Co-Author), Nicholas K. Hayward (Co-Author), Yardena Samuels^* (Last Author)

^*Corresponding author for this work

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

90 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
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 - 1 Dec 2015
Externally published	Yes

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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

@article{de4a52430a594fe9850d5689ec47d701,

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",

year = "2015",

month = dec,

day = "1",

doi = "10.1038/ng.3427",

language = "English",

volume = "47",

pages = "1408--1410",

journal = "Nature Genetics",

issn = "1061-4036",

number = "12",

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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

TY - JOUR

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

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.

UR - https://www.scopus.com/pages/publications/84949103421

U2 - 10.1038/ng.3427

DO - 10.1038/ng.3427

M3 - Article

C2 - 26502337

AN - SCOPUS:84949103421

SN - 1061-4036

VL - 47

SP - 1408

EP - 1410

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Recurrent inactivating RASA2 mutations in melanoma

Abstract

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