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Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes
Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupe...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200804/ https://www.ncbi.nlm.nih.gov/pubmed/35705541 http://dx.doi.org/10.1038/s41467-022-30694-w |
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| author | Bustoros, Mark Anand, Shankara Sklavenitis-Pistofidis, Romanos Redd, Robert Boyle, Eileen M. Zhitomirsky, Benny Dunford, Andrew J. Tai, Yu-Tzu Chavda, Selina J. Boehner, Cody Neuse, Carl Jannes Rahmat, Mahshid Dutta, Ankit Casneuf, Tineke Verona, Raluca Kastritis, Efstathis Trippa, Lorenzo Stewart, Chip Walker, Brian A. Davies, Faith E. Dimopoulos, Meletios-Athanasios Bergsagel, P. Leif Yong, Kwee Morgan, Gareth J. Aguet, François Getz, Gad Ghobrial, Irene M. |
| author_facet | Bustoros, Mark Anand, Shankara Sklavenitis-Pistofidis, Romanos Redd, Robert Boyle, Eileen M. Zhitomirsky, Benny Dunford, Andrew J. Tai, Yu-Tzu Chavda, Selina J. Boehner, Cody Neuse, Carl Jannes Rahmat, Mahshid Dutta, Ankit Casneuf, Tineke Verona, Raluca Kastritis, Efstathis Trippa, Lorenzo Stewart, Chip Walker, Brian A. Davies, Faith E. Dimopoulos, Meletios-Athanasios Bergsagel, P. Leif Yong, Kwee Morgan, Gareth J. Aguet, François Getz, Gad Ghobrial, Irene M. |
| author_sort | Bustoros, Mark |
| collection | PubMed |
| description | Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models. |
| format | Online Article Text |
| id | pubmed-9200804 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-92008042022-06-17 Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes Bustoros, Mark Anand, Shankara Sklavenitis-Pistofidis, Romanos Redd, Robert Boyle, Eileen M. Zhitomirsky, Benny Dunford, Andrew J. Tai, Yu-Tzu Chavda, Selina J. Boehner, Cody Neuse, Carl Jannes Rahmat, Mahshid Dutta, Ankit Casneuf, Tineke Verona, Raluca Kastritis, Efstathis Trippa, Lorenzo Stewart, Chip Walker, Brian A. Davies, Faith E. Dimopoulos, Meletios-Athanasios Bergsagel, P. Leif Yong, Kwee Morgan, Gareth J. Aguet, François Getz, Gad Ghobrial, Irene M. Nat Commun Article Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models. Nature Publishing Group UK 2022-06-15 /pmc/articles/PMC9200804/ /pubmed/35705541 http://dx.doi.org/10.1038/s41467-022-30694-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Bustoros, Mark Anand, Shankara Sklavenitis-Pistofidis, Romanos Redd, Robert Boyle, Eileen M. Zhitomirsky, Benny Dunford, Andrew J. Tai, Yu-Tzu Chavda, Selina J. Boehner, Cody Neuse, Carl Jannes Rahmat, Mahshid Dutta, Ankit Casneuf, Tineke Verona, Raluca Kastritis, Efstathis Trippa, Lorenzo Stewart, Chip Walker, Brian A. Davies, Faith E. Dimopoulos, Meletios-Athanasios Bergsagel, P. Leif Yong, Kwee Morgan, Gareth J. Aguet, François Getz, Gad Ghobrial, Irene M. Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| title | Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| title_full | Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| title_fullStr | Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| title_full_unstemmed | Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| title_short | Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| title_sort | genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200804/ https://www.ncbi.nlm.nih.gov/pubmed/35705541 http://dx.doi.org/10.1038/s41467-022-30694-w |
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