Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis.
Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequ...
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doaj-de594cc74d654ac9a384b971b7f9ca382020-11-25T01:26:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7218210.1371/journal.pone.0072182Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis.Valentina BoevaStéphanie JouannetRomain DaveauValérie CombaretCécile Pierre-EugèneAlex CazesCaroline Louis-BrennetotGudrun SchleiermacherSandrine FerrandGaëlle PierronAlban LermineThomas Rio FrioVirginie RaynalGilles VassalEmmanuel BarillotOlivier DelattreIsabelle Janoueix-LeroseyNeuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis.http://europepmc.org/articles/PMC3753337?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valentina Boeva Stéphanie Jouannet Romain Daveau Valérie Combaret Cécile Pierre-Eugène Alex Cazes Caroline Louis-Brennetot Gudrun Schleiermacher Sandrine Ferrand Gaëlle Pierron Alban Lermine Thomas Rio Frio Virginie Raynal Gilles Vassal Emmanuel Barillot Olivier Delattre Isabelle Janoueix-Lerosey |
spellingShingle |
Valentina Boeva Stéphanie Jouannet Romain Daveau Valérie Combaret Cécile Pierre-Eugène Alex Cazes Caroline Louis-Brennetot Gudrun Schleiermacher Sandrine Ferrand Gaëlle Pierron Alban Lermine Thomas Rio Frio Virginie Raynal Gilles Vassal Emmanuel Barillot Olivier Delattre Isabelle Janoueix-Lerosey Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. PLoS ONE |
author_facet |
Valentina Boeva Stéphanie Jouannet Romain Daveau Valérie Combaret Cécile Pierre-Eugène Alex Cazes Caroline Louis-Brennetot Gudrun Schleiermacher Sandrine Ferrand Gaëlle Pierron Alban Lermine Thomas Rio Frio Virginie Raynal Gilles Vassal Emmanuel Barillot Olivier Delattre Isabelle Janoueix-Lerosey |
author_sort |
Valentina Boeva |
title |
Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. |
title_short |
Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. |
title_full |
Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. |
title_fullStr |
Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. |
title_full_unstemmed |
Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. |
title_sort |
breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis. |
url |
http://europepmc.org/articles/PMC3753337?pdf=render |
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