Cargando…

Detection of recurrent rearrangement breakpoints from copy number data

BACKGROUND: Copy 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. Compa...

Descripción completa

Detalles Bibliográficos
Autores principales: Ritz , Anna, Paris, Pamela L, Ittmann, Michael M, Collins, Colin, Raphael, Benjamin J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112242/
https://www.ncbi.nlm.nih.gov/pubmed/21510904
http://dx.doi.org/10.1186/1471-2105-12-114
_version_ 1782205723528134656
author Ritz , Anna
Paris, Pamela L
Ittmann, Michael M
Collins, Colin
Raphael, Benjamin J
author_facet Ritz , Anna
Paris, Pamela L
Ittmann, Michael M
Collins, Colin
Raphael, Benjamin J
author_sort Ritz , Anna
collection PubMed
description BACKGROUND: Copy 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. RESULTS: We 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. CONCLUSIONS: We 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.
format Online
Article
Text
id pubmed-3112242
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-31122422011-06-12 Detection of recurrent rearrangement breakpoints from copy number data Ritz , Anna Paris, Pamela L Ittmann, Michael M Collins, Colin Raphael, Benjamin J BMC Bioinformatics Research Article BACKGROUND: Copy 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. RESULTS: We 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. CONCLUSIONS: We 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. BioMed Central 2011-04-21 /pmc/articles/PMC3112242/ /pubmed/21510904 http://dx.doi.org/10.1186/1471-2105-12-114 Text en Copyright ©2011 Ritz et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ritz , Anna
Paris, Pamela L
Ittmann, Michael M
Collins, Colin
Raphael, Benjamin J
Detection of recurrent rearrangement breakpoints from copy number data
title Detection of recurrent rearrangement breakpoints from copy number data
title_full Detection of recurrent rearrangement breakpoints from copy number data
title_fullStr Detection of recurrent rearrangement breakpoints from copy number data
title_full_unstemmed Detection of recurrent rearrangement breakpoints from copy number data
title_short Detection of recurrent rearrangement breakpoints from copy number data
title_sort detection of recurrent rearrangement breakpoints from copy number data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112242/
https://www.ncbi.nlm.nih.gov/pubmed/21510904
http://dx.doi.org/10.1186/1471-2105-12-114
work_keys_str_mv AT ritzanna detectionofrecurrentrearrangementbreakpointsfromcopynumberdata
AT parispamelal detectionofrecurrentrearrangementbreakpointsfromcopynumberdata
AT ittmannmichaelm detectionofrecurrentrearrangementbreakpointsfromcopynumberdata
AT collinscolin detectionofrecurrentrearrangementbreakpointsfromcopynumberdata
AT raphaelbenjaminj detectionofrecurrentrearrangementbreakpointsfromcopynumberdata