Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3

被引：400

作者：

Martin, Marcel ^{[1
,2
]}

Masshoefer, Lars ^{[1
]}

Temming, Petra ^{[3
]}

Rahmann, Sven ^{[1
]}

Metz, Claudia ^{[4
]}

Bornfeld, Norbert ^{[4
]}

van de Nes, Johannes ^{[5
]}

Klein-Hitpass, Ludger ^{[6
]}

Hinnebusch, Alan G. ^{[7
]}

Horsthemke, Bernhard ^{[1
]}

Lohmann, Dietmar R. ^{[1
,8
]}

Zeschnigk, Michael ^{[1
,8
]}

机构：

[1] Univ Duisburg Essen, Fac Med, Inst Human Genet, Essen, Germany

[2] Tech Univ Dortmund, Dortmund, Germany

[3] Univ Hosp Essen, Dept Pediat Haematol & Oncol, Essen, Germany

[4] Univ Duisburg Essen, Dept Ophthalmol, Fac Med, Essen, Germany

[5] Univ Duisburg Essen, Inst Pathol & Neuropathol, Fac Med, Essen, Germany

[6] Univ Duisburg Essen, Inst Cell Biol, Biochip Lab, Fac Med, Essen, Germany

[7] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, US Natl Inst Hlth, Bethesda, MD USA

[8] Univ Duisburg Essen, Eye Canc Res Grp, Fac Med, Essen, Germany

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

美国国家卫生研究院;

关键词：

MICROSATELLITE ANALYSIS; SPLICING FACTOR; INITIATION; REVEALS; BINDING; ABERRATIONS; FIDELITY; CELLS; GNAQ;

D O I：

10.1038/ng.2674

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis(1-3). Using exome sequencing, we identified recurrent somatic mutations in EIF1AX and SF3B1, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either EIF1AX (15; 48%) or SF3B1 (9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis(2). Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either SF3B1 (7; 54%) or EIF1AX (1; 8%). All EIF1AX mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19 SF3B1 mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified SF3B1 mutations in three tumors, none of which targeted Arg625.

引用

页码：933 / U296

页数：5

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