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Mutational landscape reflects the biological continuum of plasma cell dyscrasias

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 diff...

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Bibliographic Details
Main Authors: Rossi, Alessandra (Author) , Hegenbart, Ute (Author)
Format: Article (Journal)
Language:English
Published: 24 February 2017
In: Blood cancer journal
Year: 2017, Volume: 7, Issue: 2
ISSN:2044-5385
DOI:10.1038/bcj.2017.19
Online Access:Verlag, Volltext: http://dx.doi.org/10.1038/bcj.2017.19
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Author Notes:A Rossi, M Voigtlaender, S Janjetovic, B Thiele, M Alawi, M März, A Brandt, T Hansen, J Radloff, G Schön, U Hegenbart, S Schönland, C Langer, C Bokemeyer and M Binder
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Summary: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.
Item Description:Gesehen am 24.04.2018
Physical Description:Online Resource
ISSN:2044-5385
DOI:10.1038/bcj.2017.19

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