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Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups
In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognos...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092251/ https://www.ncbi.nlm.nih.gov/pubmed/29789651 http://dx.doi.org/10.1038/s41375-018-0037-9 |
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author | Bolli, Niccolo Biancon, Giulia Moarii, Matahi Gimondi, Silvia Li, Yilong de Philippis, Chiara Maura, Francesco Sathiaseelan, Vijitha Tai, Yu-Tzu Mudie, Laura O’Meara, Sarah Raine, Keiran Teague, Jon W. Butler, Adam P. Carniti, Cristiana Gerstung, Moritz Bagratuni, Tina Kastritis, Efstathios Dimopoulos, Meletios Corradini, Paolo Anderson, Kenneth C. Moreau, Philippe Minvielle, Stephane Campbell, Peter J. Papaemmanuil, Elli Avet-Loiseau, Herve Munshi, Nikhil C. |
author_facet | Bolli, Niccolo Biancon, Giulia Moarii, Matahi Gimondi, Silvia Li, Yilong de Philippis, Chiara Maura, Francesco Sathiaseelan, Vijitha Tai, Yu-Tzu Mudie, Laura O’Meara, Sarah Raine, Keiran Teague, Jon W. Butler, Adam P. Carniti, Cristiana Gerstung, Moritz Bagratuni, Tina Kastritis, Efstathios Dimopoulos, Meletios Corradini, Paolo Anderson, Kenneth C. Moreau, Philippe Minvielle, Stephane Campbell, Peter J. Papaemmanuil, Elli Avet-Loiseau, Herve Munshi, Nikhil C. |
author_sort | Bolli, Niccolo |
collection | PubMed |
description | In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication. |
format | Online Article Text |
id | pubmed-6092251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60922512018-12-10 Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups Bolli, Niccolo Biancon, Giulia Moarii, Matahi Gimondi, Silvia Li, Yilong de Philippis, Chiara Maura, Francesco Sathiaseelan, Vijitha Tai, Yu-Tzu Mudie, Laura O’Meara, Sarah Raine, Keiran Teague, Jon W. Butler, Adam P. Carniti, Cristiana Gerstung, Moritz Bagratuni, Tina Kastritis, Efstathios Dimopoulos, Meletios Corradini, Paolo Anderson, Kenneth C. Moreau, Philippe Minvielle, Stephane Campbell, Peter J. Papaemmanuil, Elli Avet-Loiseau, Herve Munshi, Nikhil C. Leukemia Article In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication. Nature Publishing Group UK 2018-05-22 2018 /pmc/articles/PMC6092251/ /pubmed/29789651 http://dx.doi.org/10.1038/s41375-018-0037-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Article Bolli, Niccolo Biancon, Giulia Moarii, Matahi Gimondi, Silvia Li, Yilong de Philippis, Chiara Maura, Francesco Sathiaseelan, Vijitha Tai, Yu-Tzu Mudie, Laura O’Meara, Sarah Raine, Keiran Teague, Jon W. Butler, Adam P. Carniti, Cristiana Gerstung, Moritz Bagratuni, Tina Kastritis, Efstathios Dimopoulos, Meletios Corradini, Paolo Anderson, Kenneth C. Moreau, Philippe Minvielle, Stephane Campbell, Peter J. Papaemmanuil, Elli Avet-Loiseau, Herve Munshi, Nikhil C. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
title | Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
title_full | Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
title_fullStr | Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
title_full_unstemmed | Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
title_short | Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
title_sort | analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092251/ https://www.ncbi.nlm.nih.gov/pubmed/29789651 http://dx.doi.org/10.1038/s41375-018-0037-9 |
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