Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes Journal Article
| Authors: | Skerget, S.; Penaherrera, D.; Chari, A.; Jagannath, S.; Siegel, D. S.; Vij, R.; Orloff, G.; Jakubowiak, A.; Niesvizky, R.; Liles, D.; Berdeja, J.; Levy, M.; Wolf, J.; Usmani, S. Z.; The MMRF CoMMpass Network; Christofferson, A. W.; Nasser, S.; Aldrich, J. L.; Legendre, C.; Benard, B.; Miller, C.; Turner, B.; Kurdoglu, A.; Washington, M.; Yellapantula, V.; Adkins, J. R.; Cuyugan, L.; Boateng, M.; Helland, A.; Kyman, S.; McDonald, J.; Reiman, R.; Stephenson, K.; Tassone, E.; Blanski, A.; Livermore, B.; Kirchhoff, M.; Rohrer, D. C.; D’Agostino, M.; Gamella, M.; Collison, K.; Stumph, J.; Kidd, P.; Donnelly, A.; Zaugg, B.; Toone, M.; McBride, K.; DeRome, M.; Rogers, J.; Craig, D.; Liang, W. S.; Gutierrez, N. C.; Jewell, S. D.; Carpten, J.; Anderson, K. C.; Cho, H. J.; Auclair, D.; Lonial, S.; Keats, J. J. |
| Contributor: | Hassoun, H. |
| Article Title: | Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes |
| Abstract: | Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation’s Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study (NCT01454297) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option. © The Author(s) 2024. |
| Keywords: | adult; cancer survival; controlled study; human tissue; aged; middle aged; human cell; major clinical study; overall survival; genetics; cancer growth; cancer immunotherapy; multiple myeloma; gene expression; gene expression profiling; cohort analysis; immunoglobulin; fibroblast growth factor receptor 3; gene expression regulation; plasma cell; gene expression regulation, neoplastic; cd20 antigen; longitudinal studies; disease progression; oncogene k ras; genetic risk; observational study; cyclin d1; ww domain containing oxidoreductase; loss of function mutation; b raf kinase; disease exacerbation; longitudinal study; interferon regulatory factor 4; personalized medicine; dna copy number variations; copy number variation; oncogene n ras; clinical outcome; early growth response factor 1; cd1 antigen; gain of function mutation; tumor necrosis factor receptor associated factor 3; humans; human; male; female; article; whole genome sequencing; exome sequencing; rna sequencing; whole exome sequencing; genetic profile; molecular fingerprinting; cd2 associated protein |
| Journal Title: | Nature Genetics |
| Volume: | 56 |
| Issue: | 9 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-01 |
| Start Page: | 1878 |
| End Page: | 1889 |
| Language: | English |
| DOI: | 10.1038/s41588-024-01853-0 |
| PUBMED: | 39160255 |
| PROVIDER: | scopus |
| PMCID: | PMC11387199 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
