Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours.
Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours.
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DOI：
10.1038/ncomms6973
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发表时间：
2015-01-22
影响因子：
16.6
通讯作者：
Turnbull, Clare
中科院分区：
文献类型：
--
作者：
Litchfield, Kevin;Summersgill, Brenda;Yost, Shawn;Sultana, Razvan;Labreche, Karim;Dudakia, Darshna;Renwick, Anthony;Seal, Sheila;Al-Saadi, Reem;Broderick, Peter;Turner, Nicholas C.;Houlston, Richard S.;Huddart, Robert;Shipley, Janet;Turnbull, Clare
睾丸生殖细胞肿瘤（TGCT）是年轻男性中最常见的癌症。在这里，我们对 42 个 TGCT 进行全外显子组测序 (WES)，以全面研究癌症的突变谱。与常见癌症相比，所有肿瘤的突变率均较低（平均每 Mb 0.5 个突变），这与 TGCT 的胚胎学起源一致。除了预期的 12p 染色体拷贝数增加和 KIT 突变之外，我们还发现肿瘤抑制基因 CDC27 中的复发突变（11.9%）。拷贝数分析揭示了精母细胞发育基因 FSIP2 (15.3%) 和 Xq28 (15.3%) 处 0.4 Mb 区域的重复扩增。两名难治性患者携带 XRCC2 突变，该基因与顺铂耐药性密切相关。我们的研究结果提供了对参与 TGCT 发生和进展的基因的进一步见解。 睾丸生殖细胞肿瘤（TGCT）是年轻男性中最常见的癌症。在这里，作者对 42 个 TGCT 的整个外显子组进行了测序，并描述了该肿瘤类型的突变谱。
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. Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here, the authors sequence the whole exomes of 42 TGCTs, and characterize the mutational profile of this tumour type.
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影响因子：
3.7
作者：
Chao HH;He X;Parker JS;Zhao W;Perou CM
通讯作者：
Perou CM
影响因子：
14.9
作者：
Gonzalez-Perez A;Lopez-Bigas N
通讯作者：
Lopez-Bigas N
影响因子：
30.8
作者：
Chung, Charles C.;Kanetsky, Peter A.;Wang, Zhaoming;Hildebrandt, Michelle A. T.;Koster, Roelof;Skotheim, Rolf I.;Kratz, Christian P.;Turnbull, Clare;Cortessis, Victoria K.;Bakken, Anne C.;Bishop, D. Timothy;Cook, Michael B.;Erickson, R. Loren;Fossa, Sophie D.;Jacobs, Kevin B.;Korde, Larissa A.;Kraggerud, Sigrid M.;Lothe, Ragnhild A.;Loud, Jennifer T.;Rahman, Nazneen;Skinner, Eila C.;Thomas, Duncan C.;Wu, Xifeng;Yeager, Meredith;Schumacher, Fredrick R.;Greene, Mark H.;Schwartz, Stephen M.;McGlynn, Katherine A.;Chanock, Stephen J.;Nathanson, Katherine L.
通讯作者：
Nathanson, Katherine L.
影响因子：
48
作者：
Gonzalez-Perez A;Perez-Llamas C;Deu-Pons J;Tamborero D;Schroeder MP;Jene-Sanz A;Santos A;Lopez-Bigas N
通讯作者：
Lopez-Bigas N
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G