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Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia

Although the pathogenesis of BCR–ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR–ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the...

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Autores principales: Iacobucci, I, Ferrarini, A, Sazzini, M, Giacomelli, E, Lonetti, A, Xumerle, L, Ferrari, A, Papayannidis, C, Malerba, G, Luiselli, D, Boattini, A, Garagnani, P, Vitale, A, Soverini, S, Pane, F, Baccarani, M, Delledonne, M, Martinelli, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317525/
https://www.ncbi.nlm.nih.gov/pubmed/22829256
http://dx.doi.org/10.1038/bcj.2012.6
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author Iacobucci, I
Ferrarini, A
Sazzini, M
Giacomelli, E
Lonetti, A
Xumerle, L
Ferrari, A
Papayannidis, C
Malerba, G
Luiselli, D
Boattini, A
Garagnani, P
Vitale, A
Soverini, S
Pane, F
Baccarani, M
Delledonne, M
Martinelli, G
author_facet Iacobucci, I
Ferrarini, A
Sazzini, M
Giacomelli, E
Lonetti, A
Xumerle, L
Ferrari, A
Papayannidis, C
Malerba, G
Luiselli, D
Boattini, A
Garagnani, P
Vitale, A
Soverini, S
Pane, F
Baccarani, M
Delledonne, M
Martinelli, G
author_sort Iacobucci, I
collection PubMed
description Although the pathogenesis of BCR–ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR–ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the complex landscape of mutations, changes in expression profiles and alternative splicing (AS) events that can be observed in such disease, the leukemia transcriptome of a BCR–ABL1-positive ALL patient at diagnosis and at relapse was sequenced using a whole-transcriptome shotgun sequencing (RNA-Seq) approach. A total of 13.9 and 15.8 million sequence reads was generated from de novo and relapsed samples, respectively, and aligned to the human genome reference sequence. This led to the identification of five validated missense mutations in genes involved in metabolic processes (DPEP1, TMEM46), transport (MVP), cell cycle regulation (ABL1) and catalytic activity (CTSZ), two of which resulted in acquired relapse variants. In all, 6390 and 4671 putative AS events were also detected, as well as expression levels for 18 315 and 18 795 genes, 28% of which were differentially expressed in the two disease phases. These data demonstrate that RNA-Seq is a suitable approach for identifying a wide spectrum of genetic alterations potentially involved in ALL.
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spelling pubmed-33175252012-04-03 Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia Iacobucci, I Ferrarini, A Sazzini, M Giacomelli, E Lonetti, A Xumerle, L Ferrari, A Papayannidis, C Malerba, G Luiselli, D Boattini, A Garagnani, P Vitale, A Soverini, S Pane, F Baccarani, M Delledonne, M Martinelli, G Blood Cancer J Original Article Although the pathogenesis of BCR–ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR–ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the complex landscape of mutations, changes in expression profiles and alternative splicing (AS) events that can be observed in such disease, the leukemia transcriptome of a BCR–ABL1-positive ALL patient at diagnosis and at relapse was sequenced using a whole-transcriptome shotgun sequencing (RNA-Seq) approach. A total of 13.9 and 15.8 million sequence reads was generated from de novo and relapsed samples, respectively, and aligned to the human genome reference sequence. This led to the identification of five validated missense mutations in genes involved in metabolic processes (DPEP1, TMEM46), transport (MVP), cell cycle regulation (ABL1) and catalytic activity (CTSZ), two of which resulted in acquired relapse variants. In all, 6390 and 4671 putative AS events were also detected, as well as expression levels for 18 315 and 18 795 genes, 28% of which were differentially expressed in the two disease phases. These data demonstrate that RNA-Seq is a suitable approach for identifying a wide spectrum of genetic alterations potentially involved in ALL. Nature Publishing Group 2012-03 2012-03-09 /pmc/articles/PMC3317525/ /pubmed/22829256 http://dx.doi.org/10.1038/bcj.2012.6 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Iacobucci, I
Ferrarini, A
Sazzini, M
Giacomelli, E
Lonetti, A
Xumerle, L
Ferrari, A
Papayannidis, C
Malerba, G
Luiselli, D
Boattini, A
Garagnani, P
Vitale, A
Soverini, S
Pane, F
Baccarani, M
Delledonne, M
Martinelli, G
Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
title Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
title_full Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
title_fullStr Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
title_full_unstemmed Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
title_short Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
title_sort application of the whole-transcriptome shotgun sequencing approach to the study of philadelphia-positive acute lymphoblastic leukemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317525/
https://www.ncbi.nlm.nih.gov/pubmed/22829256
http://dx.doi.org/10.1038/bcj.2012.6
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