Genomic organization and evolution of double minutes/homogeneously staining regions withMYCamplification in human cancer
| Autor: | Martin Dugas, Gianluca De Bellis, Angelo Lonoce, Ingrid Cifola, Gemma Macchia, Doron Tolomeo, Domenico Trombetta, Christopher W. Whelan, Marco Severgnini, Pietro D'Addabbo, Christoph Bartenhagen, Klaas Kok, Alberto L'Abbate, Lucia Carbone, Massimo Carella, Orazio Palumbo, Mariano Rocchi, Clelia Tiziana Storlazzi |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2014 |
| Předmět: |
CELL LUNG-CANCER
Genes myc Gene Expression LINES HL-60 Cells Biology Evolution Molecular Structural variation Cell Line Tumor Neoplasms C-MYC Genetics BREAST-CANCER Chromosomes Human Humans Double minute Genomic organization Chromothripsis IDENTIFICATION HUMAN-COLON Genome Human PAIRED-END Breakpoint Gene Amplification Chromosome Genomics Amplicon STRUCTURAL VARIATION DOUBLE-MINUTE CHROMOSOMES Human genome Gene Fusion Genes Neoplasm |
| Zdroj: | Nucleic Acids Research Web of Science Nucleic acids research 42 (2014): 9131–9145. doi:10.1093/nar/gku590 info:cnr-pdr/source/autori: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 Centanni Marco; Cifola, Ingrid; Dugas, Martin; Carella, Massimo; De Bellis, Gianluca; Rocchi, Mariano; Carbone, Lucia; Storlazzi, C. T./titolo:Genomic organization and evolution of double minutes%2Fhomogeneously staining regions with MYC amplification in human cancer/doi:10.1093%2Fnar%2Fgku590/rivista:Nucleic acids research/anno:2014/pagina_da:9131/pagina_a:9145/intervallo_pagine:9131–9145/volume:42 Nucleic Acids Research, 42(14), 9131-9145. Oxford University Press |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining nextgeneration sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure ofMYC-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 multistep 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. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. |
| Databáze: | OpenAIRE |
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