Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours

被引:144
作者
Litchfield, Kevin [1 ]
Summersgill, Brenda [2 ,3 ]
Yost, Shawn [1 ]
Sultana, Razvan [1 ]
Labreche, Karim [1 ,4 ]
Dudakia, Darshna [1 ]
Renwick, Anthony [1 ]
Seal, Sheila [1 ]
Al-Saadi, Reem [2 ,3 ]
Broderick, Peter [1 ]
Turner, Nicholas C. [5 ]
Houlston, Richard S. [1 ]
Huddart, Robert [6 ]
Shipley, Janet [2 ,3 ]
Turnbull, Clare [1 ,7 ]
机构
[1] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England
[2] Inst Canc Res, Div Mol Pathol, London SW3 6JB, England
[3] Inst Canc Res, Div Canc Therapeut, London SW3 6JB, England
[4] Univ Paris 06, Univ Sorbonne, CNRS, ICM,Inserm,UMR S 1127,U 1127, F-75019 Paris, France
[5] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England
[6] Inst Canc Res, Acad Radiotherapy Unit, London SW3 6JB, England
[7] Queen Mary Univ London, William Harvey Res Inst, London EC1M 6BQ, England
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
关键词
12P AMPLIFICATION; SUPPRESSOR GENE; SPERM FLAGELLUM; CANCER DRIVERS; FIBROUS SHEATH; DNA-DAMAGE; EXPRESSION; ADOLESCENTS; SEMINOMA; ADULTS;
D O I
10.1038/ncomms6973
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study the cancer's mutational profile. The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per Mb) as compared with common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT, we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4 Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT.
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页数:8
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