文章：

突变图谱反映了浆细胞异常增生的生物学连续体

Mutational landscape reflects the biological continuum of plasma cell dyscrasias

原文发布日期：2017-02-24

DOI: 10.1038/bcj.2017.19

类型: Original Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

我们对90名患者进行了下一代测序（NGS）基因面板分析，这些患者涵盖了浆细胞疾病的生物学谱系（包括意义未明的单克隆丙种球蛋白病（MGUS）、淀粉样轻链（AL）淀粉样变性和多发性骨髓瘤），使用的是未分选的骨髓样本。在该队列中，共鉴定出8个基因中的64种不同突变。NRAS（28.1%）、KRAS（21.3%）、TP53（19.5%）、BRAF（19.1%）和CCND1（8.9%）是所有患者中最常见的突变基因。非骨髓瘤浆细胞疾病患者的突变负荷显著低于骨髓瘤患者（每例0.91±0.30 vs 2.07±0.29个突变，P=0.008）。与非骨髓瘤浆细胞疾病相比，KRAS和NRAS外显子3突变与骨髓瘤队列显著相关（比值比（OR）9.87，95%置信区间（CI）1.07–90.72，P=0.043；以及OR 7.03，95% CI 1.49–33.26，P=0.014）。NRAS外显子3和TP53外显子6突变与del17p细胞遗传学显著相关（OR 0.12，95% CI 0.02–0.87，P=0.036；以及OR 0.05，95% CI 0.01–0.54，P=0.013）。我们的数据表明，突变景观反映了浆细胞疾病的生物学连续性，从MGUS和AL淀粉样变性的低复杂性突变模式到多发性骨髓瘤的高复杂性突变模式。我们的靶向NGS方法能够进行资源高效、灵敏且可扩展的突变分析，用于预后、预测或治疗目的。

原文链接：

Mutational landscape reflects the biological continuum of plasma cell dyscrasias