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Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer
The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase ch...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132716/ https://www.ncbi.nlm.nih.gov/pubmed/25034695 http://dx.doi.org/10.1093/nar/gku590 |
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author | L'Abbate, Alberto Macchia, Gemma D'Addabbo, Pietro Lonoce, Angelo Tolomeo, Doron Trombetta, Domenico Kok, Klaas Bartenhagen, Christoph Whelan, Christopher W. Palumbo, Orazio Severgnini, Marco Cifola, Ingrid Dugas, Martin Carella, Massimo De Bellis, Gianluca Rocchi, Mariano Carbone, Lucia Storlazzi, Clelia Tiziana |
author_facet | L'Abbate, Alberto Macchia, Gemma D'Addabbo, Pietro Lonoce, Angelo Tolomeo, Doron Trombetta, Domenico Kok, Klaas Bartenhagen, Christoph Whelan, Christopher W. Palumbo, Orazio Severgnini, Marco Cifola, Ingrid Dugas, Martin Carella, Massimo De Bellis, Gianluca Rocchi, Mariano Carbone, Lucia Storlazzi, Clelia Tiziana |
author_sort | L'Abbate, Alberto |
collection | PubMed |
description | The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification. |
format | Online Article Text |
id | pubmed-4132716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41327162014-12-01 Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer L'Abbate, Alberto Macchia, Gemma D'Addabbo, Pietro Lonoce, Angelo Tolomeo, Doron Trombetta, Domenico Kok, Klaas Bartenhagen, Christoph Whelan, Christopher W. Palumbo, Orazio Severgnini, Marco Cifola, Ingrid Dugas, Martin Carella, Massimo De Bellis, Gianluca Rocchi, Mariano Carbone, Lucia Storlazzi, Clelia Tiziana Nucleic Acids Res Genomics The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification. Oxford University Press 2014-08-18 2014-07-17 /pmc/articles/PMC4132716/ /pubmed/25034695 http://dx.doi.org/10.1093/nar/gku590 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genomics L'Abbate, Alberto Macchia, Gemma D'Addabbo, Pietro Lonoce, Angelo Tolomeo, Doron Trombetta, Domenico Kok, Klaas Bartenhagen, Christoph Whelan, Christopher W. Palumbo, Orazio Severgnini, Marco Cifola, Ingrid Dugas, Martin Carella, Massimo De Bellis, Gianluca Rocchi, Mariano Carbone, Lucia Storlazzi, Clelia Tiziana Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer |
title | Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer |
title_full | Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer |
title_fullStr | Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer |
title_full_unstemmed | Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer |
title_short | Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer |
title_sort | genomic organization and evolution of double minutes/homogeneously staining regions with myc amplification in human cancer |
topic | Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132716/ https://www.ncbi.nlm.nih.gov/pubmed/25034695 http://dx.doi.org/10.1093/nar/gku590 |
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