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

Nat Genet. 2015 Dec;47(12):1408-10. doi: 10.1038/ng.3427. Epub 2015 Oct 26.

Authors

Rand Arafeh¹, Nouar Qutob¹, Rafi Emmanuel¹, Alona Keren-Paz¹, Jason Madore^{2

3}, Abdel Elkahloun⁴, James S Wilmott^{2

3}, Jared J Gartner⁵, Antonella Di Pizio⁶, Sabina Winograd-Katz¹, Sivasish Sindiri⁵, Ron Rotkopf⁷, Ken Dutton-Regester⁸, Peter Johansson⁸, Antonia L Pritchard⁸, Nicola Waddell⁸, Victoria K Hill⁴, Jimmy C Lin⁵, Yael Hevroni¹, Steven A Rosenberg⁵, Javed Khan⁵, Shifra Ben-Dor⁷, Masha Y Niv⁶, Igor Ulitsky⁹, Graham J Mann^{2

3

10}, Richard A Scolyer^{2

3

11}, Nicholas K Hayward⁸, Yardena Samuels¹

Affiliations

¹ Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
² Melanoma Institute Australia, Sydney, New South Wales, Australia.
³ Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
⁴ National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.
⁵ National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
⁶ Institute of Biochemistry, Food Science and Nutrition, Hebrew University, Rehovot, Israel.
⁷ Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
⁸ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁹ Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
¹⁰ Centre for Cancer Research, Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

PMID: 26502337
PMCID: PMC4954601
DOI: 10.1038/ng.3427

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.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics*
Exome / genetics*
High-Throughput Nucleotide Sequencing / methods
Humans
Melanoma / genetics*
Melanoma / mortality
Melanoma / pathology
Mutation / genetics*
Prognosis
Skin Neoplasms / genetics*
Skin Neoplasms / mortality
Skin Neoplasms / pathology
Survival Rate
ras GTPase-Activating Proteins / genetics*

Recurrent inactivating RASA2 mutations in melanoma

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Abstract

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