Recurrent inactivating RASA2 mutations in melanoma.
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.
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Rand
R
Arafeh
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Nouar
N
Qutob
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Rafi
R
Emmanuel
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Alona
A
Keren-Paz
Melanoma Institute Australia, Sydney, New South Wales, Australia.|Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Jason
J
Madore
National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Abdel
A
Elkahloun
Melanoma Institute Australia, Sydney, New South Wales, Australia.|Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
James S
JS
Wilmott
National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Jared J
JJ
Gartner
Institute of Biochemistry, Food Science and Nutrition, Hebrew University, Rehovot, Israel.
Antonella
A
Di Pizio
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Sabina
S
Winograd-Katz
National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Sivasish
S
Sindiri
Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
Ron
R
Rotkopf
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ken
K
Dutton-Regester
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Peter
P
Johansson
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Antonia L
AL
Pritchard
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Nicola
N
Waddell
National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Victoria K
VK
Hill
National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Jimmy C
JC
Lin
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Yael
Y
Hevroni
National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Steven A
SA
Rosenberg
National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Javed
J
Khan
Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
Shifra
http://orcid.org/0000-0001-9604-1939
S
Ben-Dor
Institute of Biochemistry, Food Science and Nutrition, Hebrew University, Rehovot, Israel.
Masha Y
MY
Niv
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Igor
http://orcid.org/0000-0003-0555-6561
I
Ulitsky
Melanoma Institute Australia, Sydney, New South Wales, Australia.|Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Centre for Cancer Research, Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Graham J
GJ
Mann
Melanoma Institute Australia, Sydney, New South Wales, Australia.|Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Richard A
RA
Scolyer
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Nicholas K
NK
Hayward
Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, Israel.
Yardena
Y
Samuels
D014408:Biomarkers, Tumor / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C102193:RASA2 protein, human; D020703:ras GTPase-Activating Proteins