Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing.
Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing.
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DOI：
10.2147/ott.s86515
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发表时间：
2015
影响因子：
4
通讯作者：
Shinomura Y
中科院分区：
文献类型：
--
作者：
Ikeda H;Ishiguro K;Igarashi T;Aoki Y;Hayashi T;Ishida T;Sasaki Y;Tokino T;Shinomura Y
一名 69 岁男性于 2010 年 10 月被诊断患有 IgG λ 型多发性骨髓瘤 (MM)，II 期。他接受了一个周期的大剂量地塞米松治疗。经过三个周期的硼替佐米治疗后，患者的游离轻链水平缓慢升高，血清 M 蛋白出现新的显着升高。骨髓细胞遗传学分析揭示了恶性浆细胞的复杂核型特征。为了更好地了解该患者的分子发病机制，我们使用基于半导体的测序平台对 409 个癌症相关基因的整个编码区的突变进行了测序。测序分析显示，除了 CCND1 和 RB1 等几种拷贝数变异外，还存在 8 个非同义体细胞突变。这些改变可能在该疾病的病理学中发挥作用。这种靶向下一代测序可以预测耐药性并促进改善多发性骨髓瘤患者的治疗。
A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM), Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients.