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, Vol. 7, No. 2, 24.02.2017, p. e537.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -