Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

被引：967

作者：

Gerlinger, Marco ^{[1
]}

Horswell, Stuart ^{[2
]}

Larkin, James ^{[3
]}

Rowan, Andrew J. ^{[1
]}

Salm, Max P. ^{[2
]}

Varela, Ignacio ^{[4
]}

Fisher, Rosalie ^{[3
]}

McGranahan, Nicholas ^{[1
]}

Matthews, Nicholas ^{[5
]}

Santos, Claudio R. ^{[1
]}

Martinez, Pierre ^{[1
]}

Phillimore, Benjamin ^{[5
]}

Begum, Sharmin ^{[5
]}

Rabinowitz, Adam ^{[5
]}

Spencer-Dene, Bradley ^{[2
]}

Gulati, Sakshi ^{[2
]}

Bates, Paul A. ^{[2
]}

Stamp, Gordon ^{[2
]}

Pickering, Lisa ^{[3
]}

Gore, Martin ^{[3
]}

Nicol, David L. ^{[6
]}

Hazell, Steven ^{[7
]}

Futreal, P. Andrew ^{[8
]}

Stewart, Aengus ^{[2
]}

Swanton, Charles ^{[1
,9
]}

机构：

[1] Canc Res UK London Res Inst, Translat Canc Therapeut Lab, London WC2A 3PX, England

[2] Canc Res UK London Res Inst, London WC2A 3PX, England

[3] Royal Marsden Hosp, Dept Med, London SW3 6JJ, England

[4] Univ Cantabria, Dept Biol Mol, CSIC UC Sodercan, Inst Biomed & Biotecnol Cantabria, E-39005 Santander, Spain

[5] Canc Res UK London Res Inst, Adv Sequencing Facil, London WC2A 3PX, England

[6] Royal Marsden Hosp, Dept Urol, London SW3 6JJ, England

[7] Royal Marsden Hosp, Dept Pathol, London SW3 6JJ, England

[8] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[9] UCL, Inst Canc, London, England

来源：

NATURE GENETICS | 2014年 / 46卷 / 03期

基金：

英国医学研究理事会;

关键词：

TUMOR-SUPPRESSOR GENE; INTRATUMOR HETEROGENEITY; SOMATIC MUTATIONS; CANCER; PATTERNS; DIVERSITY; DELETIONS; PBRM1;

D O I：

10.1038/ng.2891

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73-75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development.

引用

页码：225 / +

页数：12

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