Prognostic Significance of Copy-Number Alterations in Multiple Myeloma

Avet-Loiseau, Hervé; Li, Cheng; Magrangeas, Florence; Gouraud, Wilfried; Charbonnel, Catherine; Harousseau, Jean‐Luc; Attal, Michel; Marit, Gérald; Mathiot, Claire; Façon, Thierry; Moreau, Philippe; Anderson, Kenneth C.; Campion, Loı̈c; Munshi, Nikhil C.; Minvielle, Stéphane

doi:10.1200/jco.2008.20.6136

Cited by 255 publications

(228 citation statements)

References 42 publications

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“…4). Discussion MRI pattern of marrow involvement and specific cytogenetic abnormalities have been associated with prognosis in newly diagnosed patients with symptomatic myeloma [4][5][6][7][8][9]. However, there are very limited data in the literature for the correlation between MRI patterns and cytogenetic aberrations in myeloma patients.…”

Section: Mri Patterns and Cytogenetic Abnormalitiesmentioning

confidence: 98%

“…The International Myeloma Working Group has recently suggested that the cytogenetically detected chromosomal 13 or 13q deletion, translocation t(4;14) and deletion 17p, and detection by fluorescence in situ hybridization (FISH) of t(4;14), t (14;16), and del17p are considered as poor risk features [6]. Other cytogenetic aberrations, such as the add1q21 and the hypodiploidy have also correlated with poor prognosis [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

et al. 2012

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Magnetic Resonance Imaging (MRI) and specific cytogenetic abnormalities offer important prognostic information for myeloma patients. However, limited data are available about the association between cytogenetic abnormalities and MRI patterns of marrow infiltration. To address this issue, we analyzed 228 consecutive newly diagnosed, symptomatic patients who were diagnosed and treated in a single center. On bone marrow MR images, 95 (41%) patients had diffuse, 94 (41%) had focal, 35 (15%) were normal, and 4 (1.7%) patients had variegated pattern of marrow infiltration. High risk cytogenetics were more commonly observed with diffuse MRI pattern (50% vs. 31% in focal and normal patterns). Patients with diffuse MRI pattern had poorer survival compared to others and responded better to novel agent-based therapies than to conventional chemotherapy (objective response: 88% vs. 46%, P < 0.001). There was a significant improvement of patients' survival with a diffuse MRI pattern when treated upfront with novel agents compared to conventional chemotherapy (47 vs. 24 months; P < 0.001). Diffuse MRI pattern along with ISS-3 and high risk cytogenetics could identify a very high risk group of patients with extremely poor median survival (21 months) and an only 35% probability of 3-year OS. Our study shows that symptomatic myeloma patients with a diffuse MRI pattern at diagnosis very often show high risk cytogenetic abnormalities and are benefiting from upfront novel agent-based therapies. Diffuse MRI pattern in combination with high risk cytogenetics and ISS-3 can identify a subset of myeloma patients with very poor prognosis who may need innovative treatment strategies and possibly more aggressive therapies. Am. J. Hematol. 87:861-864, 2012. V

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Section: Mri Patterns and Cytogenetic Abnormalitiesmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

et al. 2012

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“…Applications to multiple myeloma data set We next applied our method to the GWAS data from Avet-Loiseau et al 23 They performed a genome-wide analysis of malignant plasma cells from 192 multiple myeloma patients, 23 using the Affymetrix (Santa Clara, CA, USA) GeneChip Human Mapping 500K Array Set, to identify markers associated with overall survival. They provided insights into how chromosomal aberrations might have prognostic implications for multiple myeloma patients.…”

Section: Resultsmentioning

confidence: 99%

“…The NF-kB pathway was hypothesized to have lower expression among high-risk patients. 23 The cytokine network pathway has been thoroughly reviewed for prognostic and therapeutics implications in multiple myeloma, and it is also well known that cytokines have a crucial role in the disease etiology of lymphomas. 27,28 To investigate the biological plausibility of our findings, we looked at the informative SNPs in the two pathways.…”

Section: Resultsmentioning

confidence: 99%

Pathway-based identification of SNPs predictive of survival

2011

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In recent years, several association analysis methods for case-control studies have been developed. However, as we turn towards the identification of single nucleotide polymorphisms (SNPs) for prognosis, there is a need to develop methods for the identification of SNPs in high dimensional data with survival outcomes. Traditional methods for the identification of SNPs have some drawbacks. First, the majority of the approaches for case-control studies are based on single SNPs. Second, SNPs that are identified without incorporating biological knowledge are more difficult to interpret. Random forests has been found to perform well in gene expression analysis with survival outcomes. In this paper we present the first pathway-based method to correlate SNP with survival outcomes using a machine learning algorithm. We illustrate the application of pathway-based analysis of SNPs predictive of survival with a data set of 192 multiple myeloma patients genotyped for 500 000 SNPs. We also present simulation studies that show that the random forests technique with log-rank score split criterion outperforms several other machine learning algorithms. Thus, pathway-based survival analysis using machine learning tools represents a promising approach for the identification of biologically meaningful SNPs associated with disease.

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“…These translocations have been shown to be much more common among the non-hyperdiploid group compared to the hyperdiploid group. More recently, amplification of 1q21, Amp(1q21), is also thought to be associated with a poor prognosis [9,10], as well as deletion of chromosome 1p and 6q regions [11,12], while gains of chromosome 15 is common in hyperdiploid MM [13].…”

Section: Introductionmentioning

confidence: 99%

Amplification of 1q21 and Other Abnormalities in Multiple Myeloma Patients from a Tertiary Hospital in Singapore

Lim

Krishnan

Lim

et al. 2013

Indian J Hematol Blood Transfus

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Much effort has been made to stratify multiple myeloma patients for targeted therapy. However, responses have been varied and improved patient stratifications are needed. Forty-five diagnostic samples from multiple myeloma patients (median age 65 years) were stratified cytogenetically as 15 having non-hyperdiploidy, 20 having hyperdiploidy and 10 having a normal karyotype. Fluorescence in situ hybridization (FISH) assays with FGFR3/IGH, CCND1/IGH, IGH/MAF, RB1 and TP53 probes on bone marrow samples showed that IGH rearrangements were the most common abnormality in the non-hyperdiploid group but these were also found among hyperdiploid patients and patients with normal cytogenetics. Of these, FGFR3/IGH rearrangements were most frequent. Deletion of RB1/ monosomy 13 was the most common genetic abnormality across the three groups and was significantly higher among non-hyperdiploid compared to hyperdiploid patients. On the other hand, the study recorded a low incidence of TP53 deletion/monosomy 17. The FGFR3/IGH fusion was frequently seen with RB1 deletion/monosomy 13. FISH with 1p36/1q21 and 6q21/15q22 probes showed that amplification of 15q22 was seen in all of the hyperdiploid patients while amplification of 1q21, Amp(1q21), characterized nonhyperdiploid patients. In contrast, deletions of 1p36 and 6q21 were very rare events. Amp(1q21), FGFR3/IGH fusion, RB1 deletion/monosomy 13, and even TP53 deletion/monosomy 17 were seen in some hyperdiploid patients, suggesting that they have a less than favorable prognosis and require closer monitoring.

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Prognostic Significance of Copy-Number Alterations in Multiple Myeloma

Cited by 255 publications

References 42 publications

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

Pathway-based identification of SNPs predictive of survival

Amplification of 1q21 and Other Abnormalities in Multiple Myeloma Patients from a Tertiary Hospital in Singapore

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