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DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome

DIS3 gene mutations occur in roughly 10% of patients with multiple myeloma (MM); furthermore, DIS3 expression can be affected by monosomy 13 and del(13q), which occur in approximately 40% of MM cases. Despite several reports on the prevalence of DIS3 mutations, their contribution to the pathobiology...

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Autores principales: Todoerti, Katia, Ronchetti, Domenica, Favasuli, Vanessa, Maura, Francesco, Morabito, Fortunato, Bolli, Niccolò, Taiana, Elisa, Neri, Antonino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968896/
https://www.ncbi.nlm.nih.gov/pubmed/33951891
http://dx.doi.org/10.3324/haematol.2021.278342
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author Todoerti, Katia
Ronchetti, Domenica
Favasuli, Vanessa
Maura, Francesco
Morabito, Fortunato
Bolli, Niccolò
Taiana, Elisa
Neri, Antonino
author_facet Todoerti, Katia
Ronchetti, Domenica
Favasuli, Vanessa
Maura, Francesco
Morabito, Fortunato
Bolli, Niccolò
Taiana, Elisa
Neri, Antonino
author_sort Todoerti, Katia
collection PubMed
description DIS3 gene mutations occur in roughly 10% of patients with multiple myeloma (MM); furthermore, DIS3 expression can be affected by monosomy 13 and del(13q), which occur in approximately 40% of MM cases. Despite several reports on the prevalence of DIS3 mutations, their contribution to the pathobiology of MM remains largely unknown. We took advantage of the large public CoMMpass dataset to investigate the spectrum of DIS3 mutations in MM and its impact on the transcriptome and clinical outcome. We found that the clinical relevance of DIS3 mutations strictly depended on the co-occurrence of del(13q). In particular, bi-allelic DIS3 lesions significantly affected progression-free survival, independently of other predictors of poor clinical outcome, while mono-allelic events mostly affected overall survival. As expected, DIS3 mutations affect the MM transcriptome involving cellular processes and signaling pathways associated with RNA metabolism, and the deregulation of a large number of long non-coding RNA, among which we identified five distinct transcripts as independent predictors of poorer overall survival and nine of worse progression-free survival, with two (AC015982.2 and AL445228.3) predicting both unfavorable outcomes. These findings strongly prompt further studies investigating the relevance of these long non-coding RNA in MM.
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spelling pubmed-89688962022-04-11 DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome Todoerti, Katia Ronchetti, Domenica Favasuli, Vanessa Maura, Francesco Morabito, Fortunato Bolli, Niccolò Taiana, Elisa Neri, Antonino Haematologica Article DIS3 gene mutations occur in roughly 10% of patients with multiple myeloma (MM); furthermore, DIS3 expression can be affected by monosomy 13 and del(13q), which occur in approximately 40% of MM cases. Despite several reports on the prevalence of DIS3 mutations, their contribution to the pathobiology of MM remains largely unknown. We took advantage of the large public CoMMpass dataset to investigate the spectrum of DIS3 mutations in MM and its impact on the transcriptome and clinical outcome. We found that the clinical relevance of DIS3 mutations strictly depended on the co-occurrence of del(13q). In particular, bi-allelic DIS3 lesions significantly affected progression-free survival, independently of other predictors of poor clinical outcome, while mono-allelic events mostly affected overall survival. As expected, DIS3 mutations affect the MM transcriptome involving cellular processes and signaling pathways associated with RNA metabolism, and the deregulation of a large number of long non-coding RNA, among which we identified five distinct transcripts as independent predictors of poorer overall survival and nine of worse progression-free survival, with two (AC015982.2 and AL445228.3) predicting both unfavorable outcomes. These findings strongly prompt further studies investigating the relevance of these long non-coding RNA in MM. Fondazione Ferrata Storti 2021-05-06 /pmc/articles/PMC8968896/ /pubmed/33951891 http://dx.doi.org/10.3324/haematol.2021.278342 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Todoerti, Katia
Ronchetti, Domenica
Favasuli, Vanessa
Maura, Francesco
Morabito, Fortunato
Bolli, Niccolò
Taiana, Elisa
Neri, Antonino
DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
title DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
title_full DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
title_fullStr DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
title_full_unstemmed DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
title_short DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
title_sort dis3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968896/
https://www.ncbi.nlm.nih.gov/pubmed/33951891
http://dx.doi.org/10.3324/haematol.2021.278342
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