Neoplasma. 2014;61(1):48-55.
Multiple myeloma (MM) is an incurable malignant disease of the terminal developmental stage of B-lymphocytes. While genetic heterogeneity of MM is widely described, little is known about its genetic basis as well as primary damage during plasma cells (PC) development. In this study, we focused on genome-wide screening of DNA copy number changes using oligonucleotide-based array-CGH together with I-FISH of the IgH locus rearrangements in pair samples of bone marrow B-cells (CD19+) and CD138+ PC from newly diagnosed MM patients. The IgH disruption was found in 8.9% (4/45) of CD19+ samples and in 57.8% (26/45) of CD138+ samples. The genomic profiling using array-CGH identified copy number alterations (CNAs) in 10% (2/20) of CD19+ samples in regions known to be important for MM pathogenesis. In contrast, we found CNAs in 100% (16/16) of CD138+ samples. Most common chromosomal abnormalities were trisomies of odd-numbered chromosomes (3, 5, 7, 9, 11, 15, 19 and 21), gain 1q, gain Xq and monosomy of chromosome 13. We did not find any correlation between incidence of CNAs in CD19+ and CD138+ cells. In conclusion, effective utilization of FISH and array-CGH can identify genetic lesions in premalignant stages leading to better understanding and characterization of MM.
多发性骨髓瘤（MM）是 B 淋巴细胞终末发育阶段不可治愈的恶性疾病。虽然 MM 的遗传异质性得到了广泛描述，但对其遗传基础以及浆细胞（PC）发育过程中的原发性损伤知之甚少。在这项研究中，我们专注于使用寡核苷酸阵列-CGH 对新诊断的 MM 患者骨髓 B 细胞（CD19+）和 CD138+PC 配对样本的 DNA 拷贝数变化进行全基因组筛选，同时对 IgH 基因座重排进行 I-FISH。在 8.9%（4/45）的 CD19+样本和 57.8%（26/45）的 CD138+样本中发现了 IgH 断裂。使用 array-CGH 的基因组分析在 10%（2/20）的 CD19+样本中确定了已知与 MM 发病机制有关的区域的拷贝数改变（CNA）。相比之下，我们在 100%（16/16）的 CD138+样本中发现了 CNA。最常见的染色体异常是奇数染色体三体（3、5、7、9、11、15、19 和 21）、1q 增益、Xq 增益和 13 号染色体单体。我们没有发现 CD19+和 CD138+细胞中 CNA 发生率之间存在任何相关性。总之，有效利用 FISH 和 array-CGH 可以识别导致 MM 更好理解和特征描述的癌前阶段的遗传病变。
