Exploring the landscape of focal amplifications in cancer using AmpliconArchitect

被引：208

作者：

Deshpande, Viraj ^{[1
]}

Luebeck, Jens ^{[2
]}

Nguyen, Nam-Phuong D. ^{[1
]}

Bakhtiari, Mehrdad ^{[1
]}

Turner, Kristen M. ^{[3
]}

Schwab, Richard ^{[4
]}

Carter, Hannah ^{[5
,6
]}

Mischel, Paul S. ^{[3
,6
,7
]}

Bafna, Vineet ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Comp Sci & Engn, 9500 Gilman Dr, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Bioinformat & Syst Biol Program, 9500 Gilman Dr, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Sch Med, Div Hematol Oncol, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Med, Div Med Genet, 9500 Gilman Dr, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Moores Canc Ctr, 9500 Gilman Dr, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Dept Pathol, 9500 Gilman Dr, La Jolla, CA 92093 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家科学基金会;

关键词：

COMPLEX GENOMIC REARRANGEMENTS; STAINING REGIONS; IDENTIFICATION; CHROMOSOMES; EVOLUTION; DISCOVERY; BROWSER;

D O I：

10.1038/s41467-018-08200-y

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：

Focal oncogene amplification and rearrangements drive tumor growth and evolution in multiple cancer types. We present AmpliconArchitect (AA), a tool to reconstruct the fine structure of focally amplified regions using whole genome sequencing (WGS) and validate it extensively on multiple simulated and real datasets, across a wide range of coverage and copy numbers. Analysis of AA-reconstructed amplicons in a pan-cancer dataset reveals many novel properties of copy number amplifications in cancer. These findings support a model in which focal amplifications arise due to the formation and replication of extrachromosomal DNA. Applying AA to 68 viral-mediated cancer samples, we identify a large fraction of amplicons with specific structural signatures suggestive of hybrid, human-viral extrachromosomal DNA. AA reconstruction, integrated with metaphase fluorescence in situ hybridization (FISH) and PacBio sequencing on the cell-line UPCI:SCC090 confirm the extrachromosomal origin and fine structure of a Forkhead box E1 (FOXE1)-containing hybrid amplicon.

引用

页数：14

共 36 条

[1] CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing [J].

Abyzov, Alexej ;

Urban, Alexander E. ;

Snyder, Michael ;

Gerstein, Mark .

GENOME RESEARCH, 2011, 21 (06) :974-984

[2] Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability [J].

Akagi, Keiko ;

Li, Jingfeng ;

Broutian, Tatevik R. ;

Padilla-Nash, Hesed ;

Xiao, Weihong ;

Jiang, Bo ;

Rocco, James W. ;

Teknos, Theodoros N. ;

Kumar, Bhavna ;

Wangsa, Danny ;

He, Dandan ;

Ried, Thomas ;

Symer, David E. ;

Gillison, Maura L. .

GENOME RESEARCH, 2014, 24 (02) :185-199

[3] Genome rearrangements and sorting by reversals [J].

Bafna, V ;

Pevzner, PA .

SIAM JOURNAL ON COMPUTING, 1996, 25 (02) :272-289

[4] Sorting by transpositions [J].

Bafna, V ;

Pevzner, PA .

SIAM JOURNAL ON DISCRETE MATHEMATICS, 1998, 11 (02) :224-240

[5]

Chen K, 2009, NAT METHODS, V6, P677, DOI [10.1038/NMETH.1363, 10.1038/nmeth.1363]

[6] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[7] Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma [J].

deCarvalho, Ana C. ;

Kim, Hoon ;

Poisson, Laila M. ;

Winn, Mary E. ;

Mueller, Claudius ;

Cherba, David ;

Koeman, Julie ;

Seth, Sahil ;

Protopopov, Alexei ;

Felicella, Michelle ;

Zheng, Siyuan ;

Multani, Asha ;

Jiang, Yongying ;

Zhang, Jianhua ;

Nam, Do-Hyun ;

Petricoin, Emanuel F. ;

Chin, Lynda ;

Mikkelsen, Tom ;

Verhaak, Roel G. W. .

NATURE GENETICS, 2018, 50 (05) :708-+

[8] Identification of complex genomic rearrangements in cancers using CouGaR [J].

Dzamba, Misko ;

Ramani, Arun K. ;

Buczkowicz, Pawel ;

Jiang, Yue ;

Yu, Man ;

Hawkins, Cynthia ;

Brudno, Michael .

GENOME RESEARCH, 2017, 27 (01) :107-117

[9] Algebraic Distribution of Segmental Duplication Lengths in Whole-Genome Sequence Self-Alignments [J].

Gao, Kun ;

Miller, Jonathan .

PLOS ONE, 2011, 6 (07)

[10] Estimation of rearrangement phylogeny for cancer genomes [J].

Greenman, Chris D. ;

Pleasance, Erin D. ;

Newman, Scott ;

Yang, Fengtang ;

Fu, Beiyuan ;

Nik-Zainal, Serena ;

Jones, David ;

Lau, King Wai ;

Carter, Nigel ;

Edwards, Paul A. W. ;

Futreal, P. Andrew ;

Stratton, Michael R. ;

Campbelll, Peter J. .

GENOME RESEARCH, 2012, 22 (02) :346-361

← 1 2 3 4 →