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Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial
| العنوان: | Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial |
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| المؤلفون: | Croft, James, Ellis, Sidra, Sherborne, Amy L., Sharp, Kim, Price, Amy, Jenner, Matthew W., Drayson, Mark T., Owen, Roger G., Chown, Sally, Lindsay, Jindriska, Karunanithi, Kamaraj, Hunter, Hannah, Gregory, Walter M., Davies, Faith E., Morgan, Gareth J., Cook, Gordon, Atanesyan, Lilit, Savola, Suvi, Cairns, David A., Jackson, Graham, Houlston, Richard S., Kaiser, Martin F. |
| المصدر: | Leukemia; July 2021, Vol. 35 Issue: 7 p2043-2053, 11p |
| مستخلص: | Structural chromosomal changes including copy number aberrations (CNAs) are a major feature of multiple myeloma (MM), however their evolution in context of modern biological therapy is not well characterized. To investigate acquisition of CNAs and their prognostic relevance in context of first-line therapy, we profiled tumor diagnosis–relapse pairs from 178 NCRI Myeloma XI (ISRCTN49407852) trial patients using digital multiplex ligation-dependent probe amplification. CNA profiles acquired at relapse differed substantially between MM subtypes: hyperdiploid (HRD) tumors evolved predominantly in branching pattern vs. linear pattern in t(4;14) vs. stable pattern in t(11;14). CNA acquisition also differed between subtypes based on CCNDexpression, with a marked enrichment of acquired del(17p) in CCND2over CCND1tumors. Acquired CNAs were not influenced by high-dose melphalan or lenalidomide maintenance randomization. A branching evolution pattern was significantly associated with inferior overall survival (OS; hazard ratio (HR) 2.61, P= 0.0048). As an individual lesion, acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse (HR = 2.00; P= 0.021). There is an increasing need for rational therapy sequencing in MM. Our data supports the value of repeat molecular profiling to characterize disease evolution and inform management of MM relapse. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 08876924 14765551 |
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| DOI: | 10.1038/s41375-020-01096-y |