Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.
Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.
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DOI：
10.1038/nature25795
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发表时间：
2018-03-15
期刊：
影响因子：
64.8
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Ma X;Liu Y;Liu Y;Alexandrov LB;Edmonson MN;Gawad C;Zhou X;Li Y;Rusch MC;Easton J;Huether R;Gonzalez-Pena V;Wilkinson MR;Hermida LC;Davis S;Sioson E;Pounds S;Cao X;Ries RE;Wang Z;Chen X;Dong L;Diskin SJ;Smith MA;Guidry Auvil JM;Meltzer PS;Lau CC;Perlman EJ;Maris JM;Meshinchi S;Hunger SP;Gerhard DS;Zhang J
跨多种癌症类型的分子畸变分析，称为泛癌症分析，确定了来自不同谱系的癌细胞中失调的关键生物学过程的共性和差异。已对成人而非儿童癌症进行了泛癌症分析，儿童癌症通常发生在发育中胚层而非成人上皮组织中。在这里，我们提出了一个泛癌症研究的体细胞改变，包括单核苷酸变异（SNV），小插入/缺失（indels），结构变异（SV），拷贝数改变（CNA），基因融合和内部串联重复（ITD），在1,699个儿科白血病和实体瘤在六个组织型，全基因组（WGS），在统一的分析框架下处理的全外显子组（WES）和转录组（RNA-seq）测序数据（在线方法和扩展数据图1）。我们报告了儿科癌症中的142个驱动基因，其中只有45%与成人泛癌症研究中发现的基因相匹配，CNA和SV构成了大多数（62%）事件。鉴定了11个全基因组突变特征，其中一个归因于8例非整倍体白血病的紫外线暴露。34%的蛋白质编码突变可检测到突变等位基因的转录，20%表现出等位基因特异性表达。这些数据为儿科癌症提供了一个全面的基因组结构，并强调了儿科癌症特异性精确疗法开发的必要性。
Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not pediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants (SNVs), small insertion/deletions (indels), structural variations (SVs), copy number alterations (CNAs), gene fusions and internal tandem duplications (ITDs), in 1,699 pediatric leukemia and solid tumours across six histotypes, with whole-genome (WGS), whole-exome (WES) and transcriptome (RNA-seq) sequencing data processed under a uniform analytical framework (Online Methods and Extended Data Fig. 1). We report 142 driver genes in pediatric cancers, of which only 45% matched those found in adult pan-cancer studies and CNAs and SVs constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for pediatric cancers and emphasize the need for pediatric cancer-specific development of precision therapies.
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影响因子：
30.8
作者：
Holmfeldt, Linda;Wei, Lei;Diaz-Flores, Ernesto;Walsh, Michael;Zhang, Jinghui;Ding, Li;Payne-Turner, Debbie;Churchman, Michelle;Andersson, Anna;Chen, Shann-Ching;McCastlain, Kelly;Becksfort, Jared;Ma, Jing;Wu, Gang;Patel, Samir N.;Heatley, Susan L.;Phillips, Letha A.;Song, Guangchun;Easton, John;Parker, Matthew;Chen, Xiang;Rusch, Michael;Boggs, Kristy;Vadodaria, Bhavin;Hedlund, Erin;Drenberg, Christina;Baker, Sharyn;Pei, Deqing;Cheng, Cheng;Huether, Robert;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda L.;Tabib, Yashodhan;Dooling, David J.;Ochoa, Kerri;Minden, Mark;Lewis, Ian D.;To, L. Bik;Marlton, Paula;Roberts, Andrew W.;Raca, Gordana;Stock, Wendy;Neale, Geoffrey;Drexler, Hans G.;Dickins, Ross A.;Ellison, David W.;Shurtleff, Sheila A.;Pui, Ching-Hon;Ribeiro, Raul C.;Devidas, Meenakshi;Carroll, Andrew J.;Heerema, Nyla A.;Wood, Brent;Borowitz, Michael J.;Gastier-Foster, Julie M.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Downing, James R.;Hunger, Stephen P.;Loh, Mignon L.;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
16.6
作者：
Behjati S;Tarpey PS;Haase K;Ye H;Young MD;Alexandrov LB;Farndon SJ;Collord G;Wedge DC;Martincorena I;Cooke SL;Davies H;Mifsud W;Lidgren M;Martin S;Latimer C;Maddison M;Butler AP;Teague JW;Pillay N;Shlien A;McDermott U;Futreal PA;Baumhoer D;Zaikova O;Bjerkehagen B;Myklebost O;Amary MF;Tirabosco R;Van Loo P;Stratton MR;Flanagan AM;Campbell PJ
通讯作者：
Campbell PJ
影响因子：
1.7
作者：
Carnevali, Paolo;Baccash, Jonathan;Drmanac, Radoje
通讯作者：
Drmanac, Radoje
影响因子：
8.8
作者：
Chen X;Bahrami A;Pappo A;Easton J;Dalton J;Hedlund E;Ellison D;Shurtleff S;Wu G;Wei L;Parker M;Rusch M;Nagahawatte P;Wu J;Mao S;Boggs K;Mulder H;Yergeau D;Lu C;Ding L;Edmonson M;Qu C;Wang J;Li Y;Navid F;Daw NC;Mardis ER;Wilson RK;Downing JR;Zhang J;Dyer MA;St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project