Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Mikulášová, Aneta; Smetana, Jan; Wayhelova, Marketa; Janyšková, Helena; Sandecká, Viera; Kufova, Zuzana; Almáši, Martina; Jarkovský, Jiří; Gregora, Evžen; Kessler, Petr; Wróbel, Marek; Walker, Brian A.; Wardell, Christopher P.; Morgan, Gareth J.; Kuglík, Petr

doi:10.1111/ejh.12774

Cited by 27 publications

(26 citation statements)

References 42 publications

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“…Examining several thousand cancer copy-number profiles revealed 158 regions of somatic CNVs that are altered at significant frequency across multiple cancer types (17). CNVs are more frequently found in MM than MGUS, and there is a greater median number of CNVs in each MM versus MGUS patient (18). Although CNVs can be merely passenger events, some of them have an effect on MGUS progression and MM prognosis (11).…”

Section: Copy-number Variantsmentioning

confidence: 99%

“…Gain of 1q21 is more frequent in MM (40%) than in MGUS (25%; Table 1; ref. 18). It is associated with a higher risk of progression to MM in MGUS patients and with a poor prognosis in MM patients (11).…”

Section: Copy-number Variantsmentioning

confidence: 99%

“…The frequency of 1p deletions in MM is approximately 30%, opposed to only 6% in MGUS (Table 1; ref. 18). A majority of patients have interstitial deletions, but removal of the entire short arm has also been observed.…”

Section: Copy-number Variantsmentioning

confidence: 99%

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From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells

et al. 2018

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Multiple myeloma (MM) is a treatable, but incurable, malignancy of plasma cells (PC) in the bone marrow (BM). It represents the final stage in a continuum of PC dyscrasias and is consistently preceded by a premalignant phase termed monoclonal gammopathy of undetermined significance (MGUS). The existence of this well-defined premalignant phase provides the opportunity to study clonal evolution of a premalignant condition into overt cancer. Unraveling the mechanisms of malignant transformation of PC could enable early identification of MGUS patients at high risk of progression and may point to novel therapeutic targets, thereby possibly delaying or preventing malignant transformation. The MGUS-to-MM progression requires multiple genomic events and the establishment of a permissive BM microenvironment, although it is generally not clear if the various microenvironmental events are causes or consequences of disease progression. Advances in gene-sequencing techniques and the use of serial paired analyses have allowed for a more specific identification of driver lesions. The challenge in cancer biology is to identify and target those lesions that confer selective advantage and thereby drive evolution of a premalignant clone. Here, we review recent advances in the understanding of malignant transformation of MGUS to MM. .

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Section: Copy-number Variantsmentioning

confidence: 99%

Section: Copy-number Variantsmentioning

confidence: 99%

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From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells

et al. 2018

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“…This is particularly important as many of the regions are similar to the losses that are seen by FISH and chromosome analysis in myeloma such as 1p and 13q . The most common regions of CN‐LOH detected in myeloma are X, 1p, 6q, 8p, 13, 14q, 16q12‐q23, and 17 (Table ).…”

Section: Copy Number Change By Snp Microarraymentioning

confidence: 99%

Recent advances in cytogenetic characterization of multiple myeloma

Saxe

Seo

Bergeron

et al. 2018

Int J Lab Hematology

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The detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk-adapted treatment strategies. Conventional G-banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray-based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.

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“…7 Similarly, AL amyloidosis involves cytogenetically less complex plasma cells with prognostically rather favorable lesions, whereas multiple myeloma more often shows more complex and sometimes poor prognosis genetic aberrations. 8, 9, 10 …”

Section: Introductionmentioning

confidence: 99%

Mutational landscape reflects the biological continuum of plasma cell dyscrasias

Rossi

Voigtlaender

Janjetovic

et al. 2017

Blood Cancer Journal

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We subjected 90 patients covering a biological spectrum of plasma cell dyscrasias (monoclonal gammopathy of undetermined significance (MGUS), amyloid light-chain (AL) amyloidosis and multiple myeloma) to next-generation sequencing (NGS) gene panel analysis on unsorted bone marrow. A total of 64 different mutations in 8 genes were identified in this cohort. NRAS (28.1%), KRAS (21.3%), TP53 (19.5%), BRAF (19.1%) and CCND1 (8.9%) were the most commonly mutated genes in all patients. Patients with non-myeloma plasma cell dyscrasias showed a significantly lower mutational load than myeloma patients (0.91±0.30 vs 2.07±0.29 mutations per case, P=0.008). KRAS and NRAS exon 3 mutations were significantly associated with the myeloma cohort compared with non-myeloma plasma cell dyscrasias (odds ratio (OR) 9.87, 95% confidence interval (CI) 1.07–90.72, P=0.043 and OR 7.03, 95% CI 1.49–33.26, P=0.014). NRAS exon 3 and TP53 exon 6 mutations were significantly associated with del17p cytogenetics (OR 0.12, 95% CI 0.02–0.87, P=0.036 and OR 0.05, 95% CI 0.01–0.54, P=0.013). Our data show that the mutational landscape reflects the biological continuum of plasma cell dyscrasias from a low-complexity mutational pattern in MGUS and AL amyloidosis to a high-complexity pattern in multiple myeloma. Our targeted NGS approach allows resource-efficient, sensitive and scalable mutation analysis for prognostic, predictive or therapeutic purposes.

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Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Cited by 27 publications

References 42 publications

From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells

From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells

Recent advances in cytogenetic characterization of multiple myeloma

Mutational landscape reflects the biological continuum of plasma cell dyscrasias

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