Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma

Smol, Thomas; Dufour, Annika; Tricot, Sabine; Wémeau, Mathieu; Stalnikiewicz, Laure; Bernardi, Franck; Terré, Christine; Ducourneau, Benoît; Bisiau, Hervé; Daudignon, Agnès

doi:10.1186/s13039-017-0327-3

Cited by 16 publications

(10 citation statements)

References 30 publications

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“…Previous studies have found that 1q21 gain was one of the most frequent chromosomal aberrations in MM, with the occurrence rate of about 30% to 50%. 14,[21][22][23] In the present study, 1q21 gain could be identified in 39.7% of all 446 patients, which is consistent with previously published studies. Thus, the biological characteristics and prognostic effect of 1q21 gain need to be investigated.…”

Section: Discussionsupporting

confidence: 93%

Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China

Gao

Jian

et al. 2020

Cancer Medicine

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Background Autologous stem cell transplantation (ASCT) has been recommended as a standard approach for young multiple myeloma (MM) patients for decades, even in the era of novel agents. Gain of chromosome 1q21 is a common cytogenetic abnormality in MM, while its clinical prognostic value is still controversial. Methods In this multicenter study, we retrospectively analyzed 1q21 gain in 446 newly diagnosed MM patients who received at least one ASCT from three large myeloma centers in China. Results Of the all 446 patients, 1q21 gain was an adverse predictor of progression‐free survival (PFS) (34 vs 56 months, P = .005) and overall survival (OS) (69 vs 100 months, P = .002). Gain of 1q21 was more likely to coexist with t(4;14), t(14;16), and del(13q). Nevertheless, isolated 1q21 gain still exhibited unfavorable effects on PFS (35 vs 66 months, P = .045) and OS (61 vs 100 months, P = .026). The coexistence of 1q21 gain and high‐risk cytogenetics (HRCs) [del(17p), t(4;14),and/or t(14;16)] showed poor prognosis on both PFS and OS, while no additional adverse effect could be identified when compared with HRCs alone. Moreover, when coexisting with t(11;14), patients with 1q21 gain showed a comparable survival to those without 1q21 gain. For patients treated with novel induction regimens followed by ASCT, 1q21 gain also conferred an inferior prognosis. Multivariate analysis further confirmed 1q21 gain could independently predict shorter PFS and OS. Conclusion In conclusion, 1q21 gain is an adverse prognostic factor for MM patients received ASCT.

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Section: Discussionsupporting

confidence: 93%

Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China

Gao

Jian

et al. 2020

Cancer Medicine

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“…Gain of 1q21 and deletions of 17p13, 8p21, and 13q14, on the contrary, were consistently more frequently detected in subclones, suggesting a role as secondary and progression-related aberrations. Thus, the subclone architecture of plasma cell dyscrasia in AL closely resembles that in myeloma, 9,11,35,36 8,37 We conclude that the lower subclone frequency in AL amyloidosis is a reflection of the high t(11;14) frequency, as well as the universal low propensity of t(11;14) for developing genetic subclones, rather than an AL amyloidosis-specific effect.…”

Section: Discussionmentioning

confidence: 66%

Cytogenetic intraclonal heterogeneity of plasma cell dyscrasia in AL amyloidosis as compared with multiple myeloma

et al. 2018

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Analysis of intraclonal heterogeneity has yielded insights into the clonal evolution of hematologic malignancies. We compared the clonal and subclonal compositions of the underlying plasma cell dyscrasia in 544 systemic light chain amyloidosis (PC-AL) patients with 519 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or symptomatic MM; ie, PC–non-AL patients). Using interphase fluorescence in situ hybridization, subclones were stringently defined as clone size below two thirds of the largest clone and an absolute difference of ≥30%. Subclones were found less frequently in the PC-AL group, at 199 (36.6%) of 544 as compared with 267 (51.4%) of 519 in the PC–non-AL group (P < .001), and were not associated with the stage of plasma cell dyscrasia in either entity. In both groups, translocation t(11;14), other immunoglobulin heavy chain translocations, and hyperdiploidy were typically found as main clones, whereas gain of 1q21 and deletions of 8p21, 13q14, and 17p13 were frequently found as subclones. There were no shifts in the subclone/main clone ratio depending on the MGUS, SMM, or MM stage of plasma cell dyscrasia. In multivariate analysis, t(11;14) was associated with lower rates of subclone formation and hyperdiploidy with higher rates. PC-AL itself lost statistical significance, demonstrating that the lower subclone frequency in AL is a reflection of its exceptionally high t(11;14) frequency. In summary, the subclone patterns in PC-AL and PC–non-AL are closely related, implying that subclone formation depends on the main cytogenetic categories and is independent of disease entity and stage.

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“…16 Nevertheless, they rarely have been analyzed together. [17][18][19] Today, the definition of cytogenetic risk profile in patients with MM, on the basis of two or three unfavorable prognostic markers, seems restrictive and oversimplified. We aimed to adapt MM treatment to risk by defining a cytogenetic risk classification that could be used systematically (hence routinely).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma

Perrot

Lauwers‐Cancès

Tournay

et al. 2019

JCO

127

104

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PURPOSE The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM. METHODS Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients. RESULTS In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell’s concordance index greater than 70%). CONCLUSION The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.

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Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma

Cited by 16 publications

References 30 publications

Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China

Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China

Cytogenetic intraclonal heterogeneity of plasma cell dyscrasia in AL amyloidosis as compared with multiple myeloma

Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma

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