PMID- 30674876
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20231005
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 10
IP  - 1
DP  - 2019 Jan 23
TI  - Exploring the landscape of focal amplifications in cancer using 
      AmpliconArchitect.
PG  - 392
LID - 10.1038/s41467-018-08200-y [doi]
LID - 392
AB  - 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.
FAU - Deshpande, Viraj
AU  - Deshpande V
AUID- ORCID: 0000-0002-4859-9409
AD  - Department of Computer Science and Engineering, University of California at San 
      Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. virajbdeshpande@gmail.com.
FAU - Luebeck, Jens
AU  - Luebeck J
AD  - Bioinformatics and Systems Biology Program, University of California at San 
      Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
FAU - Nguyen, Nam-Phuong D
AU  - Nguyen ND
AD  - Department of Computer Science and Engineering, University of California at San 
      Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
FAU - Bakhtiari, Mehrdad
AU  - Bakhtiari M
AUID- ORCID: 0000-0001-9027-9858
AD  - Department of Computer Science and Engineering, University of California at San 
      Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
FAU - Turner, Kristen M
AU  - Turner KM
AD  - Ludwig Institute for Cancer Research, University of California at San Diego, 9500 
      Gilman Drive, La Jolla, CA, 92093, USA.
FAU - Schwab, Richard
AU  - Schwab R
AUID- ORCID: 0000-0002-0488-1226
AD  - Department of Medicine, Division of Hematology-Oncology, School of Medicine, 
      University of California at San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, 
      USA.
FAU - Carter, Hannah
AU  - Carter H
AUID- ORCID: 0000-0002-1729-2463
AD  - Department of Medicine, Division of Medical Genetics, University of California at 
      San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
AD  - Moores Cancer Center, University of California at San Diego, 9500 Gilman Drive, 
      La Jolla, CA, 92093, USA.
FAU - Mischel, Paul S
AU  - Mischel PS
AD  - Ludwig Institute for Cancer Research, University of California at San Diego, 9500 
      Gilman Drive, La Jolla, CA, 92093, USA.
AD  - Moores Cancer Center, University of California at San Diego, 9500 Gilman Drive, 
      La Jolla, CA, 92093, USA.
AD  - Department of Pathology, University of California, San Diego, 9500 Gilman Drive, 
      La Jolla, CA, 92093, USA.
FAU - Bafna, Vineet
AU  - Bafna V
AUID- ORCID: 0000-0002-5810-6241
AD  - Department of Computer Science and Engineering, University of California at San 
      Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. vbafna@cs.ucsd.edu.
LA  - eng
GR  - T32 GM008806/GM/NIGMS NIH HHS/United States
GR  - R01 HG010149/HG/NHGRI NIH HHS/United States
GR  - HG010149/NH/NIH HHS/United States
GR  - R01 NS073831/NS/NINDS NIH HHS/United States
GR  - R01GM114362/NH/NIH HHS/United States
GR  - R01 GM114362/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190123
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (FOXE1 protein, human)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Algorithms
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Chromosome Duplication
MH  - Chromosomes, Human/genetics
MH  - Computers, Molecular
MH  - Forkhead Transcription Factors/genetics
MH  - *Gene Amplification
MH  - Genes, Viral
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasms/*genetics
PMC - PMC6344493
COIS- V.B. is a co-founder, has an equity interest from Digital Proteomics, LLC (DP) 
      and receives income from DP. V.B. and P.S.M. are co-founders and V.B., V.D., and 
      P.S.M. have equity interest in Pretzel Therapeutics, Inc. (PT). The terms of 
      these arrangements have been reviewed and approved by the University of 
      California, San Diego in accordance with its conflict of interest policies. 
      Digital Proteomics and Pretzel Therapeutics were not involved in the research 
      presented here. The remaining authors declare no competing interests.
EDAT- 2019/01/25 06:00
MHDA- 2019/02/09 06:00
PMCR- 2019/01/23
CRDT- 2019/01/25 06:00
PHST- 2018/03/28 00:00 [received]
PHST- 2018/12/13 00:00 [accepted]
PHST- 2019/01/25 06:00 [entrez]
PHST- 2019/01/25 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2019/01/23 00:00 [pmc-release]
AID - 10.1038/s41467-018-08200-y [pii]
AID - 8200 [pii]
AID - 10.1038/s41467-018-08200-y [doi]
PST - epublish
SO  - Nat Commun. 2019 Jan 23;10(1):392. doi: 10.1038/s41467-018-08200-y.