Pan-cancer analysis of whole genomes

被引：1724

作者：

Campbell, Peter J. ^{[1
,2
]}

Getz, Gad ^{[3
,4
,5
,6
]}

Korbel, Jan O. ^{[7
,8
]}

Stuart, Joshua M. ^{[9
]}

Jennings, Jennifer L. ^{[10
,11
]}

Stein, Lincoln D. ^{[12
,13
]}

Perry, Marc D. ^{[14
,15
]}

Nahal-Bose, Hardeep K. ^{[15
]}

Ouellette, B. F. Francis ^{[16
,17
]}

Li, Constance H. ^{[12
,18
]}

Rheinbay, Esther ^{[3
,6
,19
]}

Nielsen, G. Petur ^{[19
]}

Sgroi, Dennis C. ^{[19
]}

Wu, Chin-Lee ^{[19
]}

Faquin, William C. ^{[19
]}

Deshpande, Vikram ^{[19
]}

Boutros, Paul C. ^{[12
,18
,20
,21
]}

Lazar, Alexander J. ^{[22
,23
]}

Hoadley, Katherine A. ^{[24
,25
]}

Louis, David N. ^{[19
]}

Dursi, L. Jonathan ^{[12
,26
]}

Yung, Christina K. ^{[15
]}

Bailey, Matthew H. ^{[27
,28
]}

Saksena, Gordon ^{[3
]}

Raine, Keiran M. ^{[1
]}

Buchhalter, Ivo ^{[29
,30
,31
,32
]}

Kleinheinz, Kortine ^{[29
,31
,32
]}

Schlesner, Matthias ^{[29
,33
]}

Zhang, Junjun ^{[15
]}

Wang, Wenyi ^{[34
]}

Wheeler, David A. ^{[35
,36
]}

Ding, Li ^{[27
,28
,37
]}

Simpson, Jared T. ^{[12
,38
]}

O'Connor, Brian D. ^{[15
,39
]}

Yakneen, Sergei ^{[8
]}

Ellrott, Kyle ^{[40
]}

Miyoshi, Naoki ^{[41
]}

Butler, Adam P. ^{[1
]}

Royo, Romina ^{[42
]}

Shorser, Solomon, I ^{[12
]}

Vazquez, Miguel ^{[42
,43
]}

Rausch, Tobias ^{[8
]}

Tiao, Grace ^{[3
]}

Waszak, Sebastian M. ^{[8
]}

Rodriguez-Martin, Bernardo ^{[44
,45
,46
]}

Shringarpure, Suyash ^{[47
]}

Wu, Dai-Ying ^{[48
]}

Demidov, German M. ^{[49
,50
,51
]}

Delaneau, Olivier ^{[52
,53
,54
]}

Hayashi, Shuto ^{[41
]}

机构：

[1] Wellcome Sanger Inst, Hinxton, England

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

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[6] Harvard Med Sch, Boston, MA 02115 USA

[7] European Bioinformat Inst EMBL, European Mol Biol Lab EMBL EBI, Hinxton, England

[8] European Mol Biol Lab EMBL, Genome Biol Unit, Heidelberg, Germany

[9] Univ Calif Santa Cruz, Biomol Engn Dept, Santa Cruz, CA 95064 USA

[10] Ontario Inst Canc Res, Adapt Oncol Initiat, Toronto, ON, Canada

[11] ICGC Accelerating Res Genom Oncol ICGC ARGO Secre, Int Canc Genome Consortium ICGC, Toronto, ON, Canada

[12] Ontario Inst Canc Res, Computat Biol Program, Toronto, ON, Canada

[13] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[14] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA

[15] Ontario Inst Canc Res, Genome Informat Program, Toronto, ON, Canada

[16] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada

[17] Ontario Inst Canc Res, Genome Informat, Toronto, ON, Canada

[18] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[19] Massachusetts Gen Hosp, Boston, MA 02114 USA

[20] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada

[21] Univ Calif Los Angeles, Los Angeles, CA USA

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

[23] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Dept Translat Mol Pathol, Houston, TX 77030 USA

[24] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[25] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

[26] Hosp Sick Children, Toronto, ON, Canada

[27] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA

[28] Washington Univ, McDonnell Genome Inst, St Louis, MO 63110 USA

[29] German Canc Res Ctr, Div Theoret Bioinformat, Heidelberg, Germany

[30] German Canc Res Ctr, Heidelberg Ctr Personalized Oncol DKFZ HIPO, Heidelberg, Germany

[31] Heidelberg Univ, Inst Pharm & Mol Biotechnol, Heidelberg, Germany

[32] Heidelberg Univ, BioQuant, Heidelberg, Germany

[33] German Canc Res Ctr, Bioinformat & Omics Data Analyt, Heidelberg, Germany

[34] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[35] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[36] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[37] Washington Univ, Dept Genet & Dept Med, St Louis, MO 63110 USA

[38] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada

[39] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA

[40] Oregon Hlth & Sci Univ, Computat Biol Program, Portland, OR 97201 USA

[41] Univ Tokyo, Inst Med Sci, Tokyo, Japan

[42] Barcelona Supercomp Ctr BSC, Barcelona, Spain

[43] Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Dept Clin & Mol Med, Trondheim, Norway

[44] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CiMUS, Santiago De Compostela, Spain

[45] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CiMUS, Dept Zool Genet & Phys Anthropol, Santiago De Compostela, Spain

[46] Univ Vigo, Biomed Res Ctr CINBIO, Vigo, Spain

[47] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[48] Annai Syst, Carlsbad, CA USA

[49] Barcelona Inst Sci & Technol BIST, Ctr Genom Regulat CRG, Barcelona, Spain

[50] Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany

来源：

NATURE | 2020年 / 578卷 / 7793期

关键词：

TERT PROMOTER MUTATIONS; SOMATIC MUTATIONS; COMPREHENSIVE CHARACTERIZATION; SYSTEMATIC ANALYSIS; DNA-DAMAGE; LANDSCAPE; SIGNATURES; REARRANGEMENTS; EVOLUTION; PATTERNS;

D O I：

10.1038/s41586-020-1969-6

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：

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).

引用

页码：82 / +

页数：50

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