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• W2555719318 abstract "The genomic alterations associated with cancers are numerous and varied, involving both isolated and large-scale complex genomic rearrangements (CGRs). Although the underlying mechanisms are not well understood, CGRs have been implicated in tumorigenesis. Here, we introduce CouGaR, a novel method for characterizing the genomic structure of amplified CGRs, leveraging both depth of coverage (DOC) and discordant pair-end mapping techniques. We applied our method to whole-genome sequencing (WGS) samples from The Cancer Genome Atlas and identify amplified CGRs in at least 5.2% (10+ copies) to 17.8% (6+ copies) of the samples. Furthermore, ∼95% of these amplified CGRs contain genes previously implicated in tumorigenesis, indicating the importance and widespread occurrence of CGRs in cancers. Additionally, CouGaR identified the occurrence of ‘chromoplexy’ in nearly 63% of all prostate cancer samples and 30% of all bladder cancer samples. To further validate the accuracy of our method, we experimentally tested 17 predicted fusions in two pediatric glioma samples and validated 15 of these (88%) with precise resolution of the breakpoints via qPCR experiments and Sanger sequencing, with nearly perfect copy count concordance. Additionally, to further help display and understand the structure of CGRs, we have implemented CouGaR-viz, a generic stand-alone tool for visualization of the copy count of regions, breakpoints, and relevant genes." @default.
• W2555719318 created "2016-11-30" @default.
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• W2555719318 date "2016-11-14" @default.
• W2555719318 modified "2023-10-16" @default.
• W2555719318 title "Identification of complex genomic rearrangements in cancers using CouGaR" @default.
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• W2555719318 doi "https://doi.org/10.1101/gr.211201.116" @default.
• W2555719318 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5204335" @default.
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• W2555719318 hasPublicationYear "2016" @default.
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