AI Article Synopsis
- Focal oncogene amplification and rearrangements are key drivers of tumor growth in various cancers, and the study introduces a new tool called AmpliconArchitect (AA) for analyzing these amplified regions through whole genome sequencing (WGS).
- AA has been thoroughly tested on both simulated and real datasets, uncovering new characteristics of copy number amplifications across multiple cancer types, which supports the idea that these amplifications are linked to the formation and replication of extrachromosomal DNA.
- In exploring 68 viral-mediated cancer samples, AA detected amplicons with unique structural features indicating a mix of human and viral DNA, confirming their extrachromosomal nature and the detailed structure of a specific hybrid am
Article Abstract
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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344493 | PMC |
| http://dx.doi.org/10.1038/s41467-018-08200-y | DOI Listing |
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