Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial
| Autor: | James Croft, Hannah Hunter, Richard S. Houlston, Amy Price, David A Cairns, Jindriska Lindsay, Matthew W Jenner, Gordon Cook, Suvi Savola, Kamaraj Karunanithi, Mark T. Drayson, Gareth J. Morgan, Lilit Atanesyan, Amy L. Sherborne, Walter M Gregory, Martin Kaiser, Sidra Ellis, Roger G. Owen, Kim Sharp, Sally Chown, Graham Jackson, Faith E. Davies |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Melphalan Cancer Research medicine.medical_specialty Randomization DNA Copy Number Variations Nerve Tissue Proteins Myeloma Article Lesion Text mining Recurrence Internal medicine Genetics research Cancer genomics medicine Humans Cyclin D1 Copy number aberration Lenalidomide Multiple myeloma business.industry Hazard ratio Hematology Prognosis medicine.disease medicine.symptom Multiple Myeloma business medicine.drug |
| Zdroj: | Leukemia |
| ISSN: | 0887-6924 |
| Popis: | 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 CCND expression, with a marked enrichment of acquired del(17p) in CCND2 over CCND1 tumors. 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. |
| Databáze: | OpenAIRE |
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