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Mutational landscape reflects the biological continuum of plasma cell dyscrasias

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Mutational landscape reflects the biological continuum of plasma cell dyscrasias. / Rossi, Alessandra ; Voigtländer, Minna; Janjetovic, S; Thiele, B; Alawi, M; März, M; Brandt, A; Hansen, T; Radloff, J; Schön, G; Hegenbart, U; Schönland, Stefan; Langer, C; Bokemeyer, C; Binder, M.

in: BLOOD CANCER J, Jahrgang 7, Nr. 2, 24.02.2017, S. e537.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rossi, A, Voigtländer, M, Janjetovic, S, Thiele, B, Alawi, M, März, M, Brandt, A, Hansen, T, Radloff, J, Schön, G, Hegenbart, U, Schönland, S, Langer, C, Bokemeyer, C & Binder, M 2017, 'Mutational landscape reflects the biological continuum of plasma cell dyscrasias', BLOOD CANCER J, Jg. 7, Nr. 2, S. e537. https://doi.org/10.1038/bcj.2017.19

APA

Rossi, A., Voigtländer, M., Janjetovic, S., Thiele, B., Alawi, M., März, M., Brandt, A., Hansen, T., Radloff, J., Schön, G., Hegenbart, U., Schönland, S., Langer, C., Bokemeyer, C., & Binder, M. (2017). Mutational landscape reflects the biological continuum of plasma cell dyscrasias. BLOOD CANCER J, 7(2), e537. https://doi.org/10.1038/bcj.2017.19

Vancouver

Rossi A, Voigtländer M, Janjetovic S, Thiele B, Alawi M, März M et al. Mutational landscape reflects the biological continuum of plasma cell dyscrasias. BLOOD CANCER J. 2017 Feb 24;7(2):e537. https://doi.org/10.1038/bcj.2017.19

Bibtex

@article{994a7f633ece45788d1cf0272f842ed2,
title = "Mutational landscape reflects the biological continuum of plasma cell dyscrasias",
abstract = "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.",
author = "Alessandra Rossi and Minna Voigtl{\"a}nder and S Janjetovic and B Thiele and M Alawi and M M{\"a}rz and A Brandt and T Hansen and J Radloff and G Sch{\"o}n and U Hegenbart and Stefan Sch{\"o}nland and C Langer and C Bokemeyer and M Binder",
year = "2017",
month = feb,
day = "24",
doi = "10.1038/bcj.2017.19",
language = "English",
volume = "7",
pages = "e537",
journal = "BLOOD CANCER J",
issn = "2044-5385",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Mutational landscape reflects the biological continuum of plasma cell dyscrasias

AU - Rossi, Alessandra

AU - Voigtländer, Minna

AU - Janjetovic, S

AU - Thiele, B

AU - Alawi, M

AU - März, M

AU - Brandt, A

AU - Hansen, T

AU - Radloff, J

AU - Schön, G

AU - Hegenbart, U

AU - Schönland, Stefan

AU - Langer, C

AU - Bokemeyer, C

AU - Binder, M

PY - 2017/2/24

Y1 - 2017/2/24

N2 - 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.

AB - 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.

U2 - 10.1038/bcj.2017.19

DO - 10.1038/bcj.2017.19

M3 - SCORING: Journal article

C2 - 28234344

VL - 7

SP - e537

JO - BLOOD CANCER J

JF - BLOOD CANCER J

SN - 2044-5385

IS - 2

ER -