Recurrent inactivating RASA2 mutations in melanoma

被引：81

作者：

Arafeh, Rand ^{[1
]}

Qutob, Nouar ^{[1
]}

Emmanuel, Rafi ^{[1
]}

Keren-Paz, Alona ^{[1
]}

Madore, Jason ^{[2
,3
]}

Elkahloun, Abdel ^{[4
]}

Wilmott, James S. ^{[2
,3
]}

Gartner, Jared J. ^{[5
]}

Di Pizio, Antonella ^{[6
]}

Winograd-Katz, Sabina ^{[1
]}

Sindiri, Sivasish ^{[5
]}

Rotkopf, Ron ^{[7
]}

Dutton-Regester, Ken ^{[8
]}

Johansson, Peter ^{[8
]}

Pritchard, Antonia L. ^{[8
]}

Waddell, Nicola ^{[8
]}

Hill, Victoria K. ^{[4
]}

Lin, Jimmy C. ^{[5
]}

Hevroni, Yael ^{[1
]}

Rosenberg, Steven A. ^{[5
]}

Khan, Javed ^{[5
]}

Ben-Dor, Shifra ^{[7
]}

Niv, Masha Y. ^{[6
]}

Ulitsky, Igor ^{[9
]}

Mann, Graham J. ^{[2
,3
,10
]}

Scolyer, Richard A. ^{[2
,3
,11
]}

Hayward, Nicholas K. ^{[8
]}

Samuels, Yardena ^{[1
]}

机构：

[1] Weizmann Inst Sci, Mol Cell Biol Dept, IL-76100 Rehovot, Israel

[2] Melanoma Inst Australia, Sydney, NSW, Australia

[3] Univ Sydney, Sydney Med Sch, Discipline Pathol, Sydney, NSW 2006, Australia

[4] NHGRI, US NIH, Bethesda, MD 20892 USA

[5] NCI, US NIH, Bethesda, MD 20892 USA

[6] Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, IL-76100 Rehovot, Israel

[7] Weizmann Inst Sci, Dept Biol Serv, IL-76100 Rehovot, Israel

[8] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[9] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

[10] Univ Sydney, Westmead Millennium Inst Med Res, Ctr Canc Res, Sydney, NSW 2006, Australia

[11] Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia

来源：

NATURE GENETICS | 2015年 / 47卷 / 12期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 欧洲研究理事会; 以色列科学基金会;

关键词：

METASTATIC MELANOMA; CANCER; BRAF; INTEGRATION; MUTANTS; REVEALS;

D O I：

10.1038/ng.3427

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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.

引用

页码：1408 / +

页数：5

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