Detection of recurrent rearrangement breakpoints from copy number data

BMC Bioinformatics

Research Article

Anna Ritz¹  Benjamin J Raphael²  Michael M Ittmann³  Pamela L Paris⁴  Colin Collins⁵ 

[1] Department of Computer Science, Brown University, Providence, RI, USA;Department of Computer Science, Brown University, Providence, RI, USA;Center for Computational Molecular Biology, Brown University, Providence, RI, USA;Department of Pathology, Baylor College of Medicine, Houston, TX, USA;Department of Urology, University of California at San Francisco, San Francisco, CA, USA;Vancouver Prostate Centre, Vancouver, BC, Canada;

关键词: Fusion Gene;    Copy Number Change;    Test Genome;    Copy Number Profile;    Copy Number Data;   

DOI  :  10.1186/1471-2105-12-114

 received in 2010-08-30, accepted in 2011-04-21,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundCopy number variants (CNVs), including deletions, amplifications, and other rearrangements, are common in human and cancer genomes. Copy number data from array comparative genome hybridization (aCGH) and next-generation DNA sequencing is widely used to measure copy number variants. Comparison of copy number data from multiple individuals reveals recurrent variants. Typically, the interior of a recurrent CNV is examined for genes or other loci associated with a phenotype. However, in some cases, such as gene truncations and fusion genes, the target of variant lies at the boundary of the variant.ResultsWe introduce Neighborhood Breakpoint Conservation (NBC), an algorithm for identifying rearrangement breakpoints that are highly conserved at the same locus in multiple individuals. NBC detects recurrent breakpoints at varying levels of resolution, including breakpoints whose location is exactly conserved and breakpoints whose location varies within a gene. NBC also identifies pairs of recurrent breakpoints such as those that result from fusion genes. We apply NBC to aCGH data from 36 primary prostate tumors and identify 12 novel rearrangements, one of which is the well-known TMPRSS2-ERG fusion gene. We also apply NBC to 227 glioblastoma tumors and predict 93 novel rearrangements which we further classify as gene truncations, germline structural variants, and fusion genes. A number of these variants involve the protein phosphatase PTPN12 suggesting that deregulation of PTPN12, via a variety of rearrangements, is common in glioblastoma.ConclusionsWe demonstrate that NBC is useful for detection of recurrent breakpoints resulting from copy number variants or other structural variants, and in particular identifies recurrent breakpoints that result in gene truncations or fusion genes. Software is available at http://http.//cs.brown.edu/people/braphael/software.html.

【 授权许可】

CC BY   
© Ritz et al; licensee BioMed Central Ltd. 2011