Exploring the landscape of focal amplifications in cancer using AmpliconArchitect.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 01 2019
23 01 2019
Historique:
received:
28
03
2018
accepted:
13
12
2018
entrez:
25
1
2019
pubmed:
25
1
2019
medline:
9
2
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30674876
doi: 10.1038/s41467-018-08200-y
pii: 10.1038/s41467-018-08200-y
pmc: PMC6344493
doi:
Substances chimiques
FOXE1 protein, human
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
392Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008806
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010149
Pays : United States
Organisme : NIH HHS
ID : HG010149
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS073831
Pays : United States
Organisme : NIH HHS
ID : R01GM114362
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114362
Pays : United States
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