Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics
Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics
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DOI：
10.1002/gcc.20231
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发表时间：
2005-10-01
影响因子：
3.7
通讯作者：
Jauch, A
中科院分区：
文献类型：
--
作者：
Cremer, FW;Bila, J;Jauch, A
为了描述多发性骨髓瘤（MM）的亚群及其克隆演变，我们分析了81例新诊断的患者间期荧光原位杂交使用一个全面的探针集10条染色体和两个IGH重排。每例患者5个探针的中位数显示异常信号数（范围，1-10）。最常见的额外拷贝是15 q22，19 q13，9 q34，11 q23和1 q21。通常观察到的损失是13 q 14.3，17 p 13和22 q 11。通过拷贝数评分（CS）对每例患者的增益或损失优势进行量化。通过绘制对应于超二倍体和非超二倍体MM的患者拷贝数分数与CS值的关系图，发现两个峰（CS = +3和CS = 0）。聚类分析揭示了四个主要分支：（i）9 q、15 q、19 q和/或11 q的增加;（ii）13 q和t（4; 14）的缺失;（iii）t（11; 14）;和（iv）1 q的增加。肿瘤发生树的统计学建模表明，早期独立事件是15 q/9 q和/或11 q，t（11; 14）的增加; 13 q缺失，随后是t（4; 14）;以及1 q的增加。17 p13、22 q11、8 p12和6 q21的畸变被发现为后续事件。I q增加的MM被描述为β 2-微球蛋白水平显著升高和血红蛋白水平降低的亚实体，表明预后不良。从我们的研究结果，我们提出了一个模型的MM克隆进化。(c)2005 Wiley-Liss，Inc.
To delineate multiple myeloma (MM) subgroups and their clonal evolution, we analyzed 81 newly diagnosed patients by interphase fluorescence in situ hybridization using a comprehensive probe set for 10 chromosomes and two IGH rearrangements. A median of 5 probes per patient displayed aberrant signal numbers (range, 1-10). Additional copies most frequently found were for 15q22, 19q13, 9q34, 11q23, and 1q21. Losses commonly observed were of 13q 14.3, 17p 13, and 22q 11. Predominance of gain or loss was quantified by a copy number score (CS) for each patient. Two peaks (CS = +3 and CS = 0) were found by plotting patient copy number scores over CS values corresponding to hyperdiploid and nonhyperdiploid MM. Cluster analysis revealed four major branches: (i) gain of 9q, 15q, 19q, and/or 11q; (ii) deletion of 13q and t(4; 14); (iii) t(11; 14); and (iv) gain of 1q. Statistical modeling of an oncogenetic tree indicated that early independent events were gain of 15q/9q and/or 11q, t(11; 14); deletion of 13q followed by t(4; 14); and gain of 1q. Aberrations of 17p13, 22q11, 8p12, and 6q21 were found as subsequent events. MM with gain of I q was delineated as a subentity with significantly higher beta-2-microglobulin and lower hemoglobin levels, indicating a poor prognosis. From our results, we propose a model of MM for clonal evolution. (c) 2005 Wiley-Liss, Inc.