Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma

被引：153

作者：

Tarpey, Patrick S. ^{[1
]}

Behjati, Sam ^{[1
,2
]}

Cooke, Susanna L. ^{[1
]}

Van Loo, Peter ^{[1
,3
,4
]}

Wedge, David C. ^{[1
]}

Pillay, Nischalan ^{[5
,6
]}

Marshall, John ^{[1
]}

O'Meara, Sarah ^{[1
]}

Davies, Helen ^{[1
]}

Nik-Zainal, Serena ^{[1
]}

Beare, David ^{[1
]}

Butler, Adam ^{[1
]}

Gamble, John ^{[1
]}

Hardy, Claire ^{[1
]}

Hinton, Jonathon ^{[1
]}

Jia, Ming Ming ^{[1
]}

Jayakumar, Alagu ^{[1
]}

Jones, David ^{[1
]}

Latimer, Calli ^{[1
]}

Maddison, Mark ^{[1
]}

Martin, Sancha ^{[1
]}

McLaren, Stuart ^{[1
]}

Menzies, Andrew ^{[1
]}

Mudie, Laura ^{[1
]}

Raine, Keiran ^{[1
]}

Teague, Jon W. ^{[1
]}

Tubio, Jose M. C. ^{[1
]}

Halai, Dina ^{[5
]}

Tirabosco, Roberto ^{[5
]}

Amary, Fernanda ^{[5
]}

Campbell, Peter J. ^{[1
,7
,8
]}

Stratton, Michael R. ^{[1
]}

Flanagan, Adrienne M. ^{[5
,6
]}

Futreal, P. Andrew ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England

[2] Univ Cambridge, Dept Paediat, Cambridge, England

[3] VIB, Dept Human Genet, Human Genome Lab, Louvain, Belgium

[4] Katholieke Univ Leuven, Louvain, Belgium

[5] Royal Natl Orthopaed Hosp Natl Hlth Serv NHS Trus, Stanmore, Middx, England

[6] UCL, Inst Canc, London, England

[7] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 2QQ, England

[8] Univ Cambridge, Dept Haematol, Cambridge, England

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

英国惠康基金;

关键词：

RECEPTOR; PATHWAY; CANCER; TUMORS; MICE;

D O I：

10.1038/ng.2668

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).

引用

页码：923 / U293

页数：5

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