Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis

Davies, Faith E.; Dring, Ann; Li, Cheng; Rawstron, Andy C.; Shammas, Masood A.; O'Connor, Sheila M.; Fenton, James A. L.; Hideshima, Teru; Chauhan, Dharminder; Tai, Isabella T.; Robinson, Elizabeth A.; Auclair, Daniel; Rees, Karen; González, David; Ashcroft, A. John; Dasgupta, Ranjit; Mitsiades, Constantine S.; Mitsiades, Nicholas; Chen, Lan B.; Wong, Wing Hung; Munshi, Nikhil C.; Morgan, Gareth J.; Anderson, Kenneth C.

doi:10.1182/blood-2003-01-0016

Cited by 204 publications

(155 citation statements)

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“…PC bearing CNA increase from MGUS to SMM and to MM We observed at least one minor subclone (o50% of PC) carrying a CNA more frequently in MGUS (75% of cases; median of 3.5 of subclones/case, range 1-12) than in SMM (30% of cases; median of 1, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and MM (56% of cases; median of 1/case, range 1-16) (P ¼ 0.017 in the comparison of MGUS vs SMM þ MM). When we compared the presence of minor and major subclones for a particular CNA, we observed that the minor subclones predominated in MGUS, whereas in MM patients (both symptomatic and asymptomatic disease) the major subpopulation was the predominant one.…”

Section: Quality Assessment Of Snp Arraysmentioning

confidence: 70%

“…6 The current pathogenic models assume that MM develops through a multistep transformation from normal PC to MGUS, which implies PC immortalization and, subsequently, the transformation to active MM, where clonal PC cause end-organ damage. 7,8 Cytogenetic studies using fluorescence in situ hybridization (FISH) have demonstrated that most genetic lesions typical of MM are already present in MGUS stage. [9][10][11] We recently have shown that a major difference between these three entities is the number of PC with genetic abnormalities, which increases from MGUS to SMM and to MM.…”

Section: Multiple Myeloma (Mm) Is a Malignant Disorder Characterized mentioning

confidence: 99%

“…The only five cases with no CNA were from asymptomatic entities (two MGUS and three SMM patients), whereas all MM patients showed at least one CNA. Overall, a total of 703 DNA copy number changes were detected with a median of 8 imbalances per abnormal case (range, 1-32 imbalances): 374 gains with a median of 4 per abnormal case (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 329 losses with a median of 3 (range . A detailed description of the most frequent aberrations is shown in Supplementary Table 2.…”

Section: Quality Assessment Of Snp Arraysmentioning

confidence: 99%

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SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

et al. 2012

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Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P ¼ 0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P ¼ 0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

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Section: Quality Assessment Of Snp Arraysmentioning

confidence: 70%

Section: Multiple Myeloma (Mm) Is a Malignant Disorder Characterized mentioning

confidence: 99%

Section: Quality Assessment Of Snp Arraysmentioning

confidence: 99%

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SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

et al. 2012

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“…Gene expression profiling of patients with MM and MGUS has revealed well-defined mRNA expression patterns (De Vos et al, 2002;Zhan et al, 2002;Davies et al, 2003). However, while MGUS and MM plasma cells can be distinguished from normal plasma cells, they are difficult to differentiate from each other.…”

Section: Angiogenic-related Genes In Multiple Myelomamentioning

confidence: 99%

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

2006

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Tumor microenvironment is essential for tumor cell proliferation, angiogenesis, invasion and metastasis through its provision of survival signals, secretion of growth and pro-angiogenic factors, and direct adhesion molecule interactions. This review examines its importance in the induction of an angiogenic response in multiple myeloma (MM). The encouraging results of preclinical and clinical trials in which MM has been treated by targeting the tumor microenvironment are also discussed.

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“…Already we have begun to gain insight into the multistep transformation of MGUS to MM using gene expression profiling. 4 The next level of prognostic classification of MGUS will depend on the results of such expressionprofiling studies. Until such time that the underlying molecular defects responsible for the transformation are understood, the current study provides a clinically meaningful way to categorize patients with significantly different biological behavior.…”

Section: Determining the Undetermined -------------------------------mentioning

confidence: 99%

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2005

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Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis

Cited by 204 publications

References 25 publications

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

Determining the undetermined

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