Chromosomal imbalances in diffuse large B-cell lymphoma detected by comparative genomic hybridization
Chromosomal imbalances in diffuse large B-cell lymphoma detected by comparative genomic hybridization
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DOI：
10.1097/01.mp.0000024375.04135.2b
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发表时间：
2002-08-01
期刊：
影响因子：
7.5
通讯作者：
Lagercrantz, S
中科院分区：
文献类型：
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作者：
Berglund, M;Enblad, G;Lagercrantz, S
弥漫性大b细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤。与许多其他血液系统恶性肿瘤不同，DLBCL中未发现具有诊断或预后价值的染色体异常。通过比较基因组杂交（CGH）对来自40例患者的54例DLBCL肿瘤进行了数值染色体失衡的表征。通过IGH基因重排分析和/或CGH谱，在11对匹配的诊断肿瘤及其复发中证实了9对克隆相关性。此外，对所有病例进行BCL2和BCL6/LAZ3的免疫组化表达分析。在94%的诊断性肿瘤样本和所有复发病例中检测到拷贝数变化。在诊断性肿瘤中，染色体缺失优先见于8p22-pter（29%）、1p34-pter（26%）、6q23-qter（20%）、17p12-pter（17%）和22q（17%）、9p23-pter(14%)，而染色体缺失主要见于Xq25-26（43%）、13q22（26%）、12cen-q14（20%）、3q24-25（11%）、7（11%）和18q12-21（11%）。22q的缺失在临床分期越晚期的诊断性肿瘤样本中更为常见，换句话说，III-IV期与I-II期相比，18q21条带的缺失在复发肿瘤中比在诊断性肿瘤中更为常见。这些复发性改变均未被检测为单一异常，这表明低于CGH检测水平的其他遗传病变可能是DLBCL肿瘤发生的起始事件。然而，CGH改变的分布支持遗传事件进展的观点，其中8p和9p的丢失以及3q、13q和18q的获得将代表相对早期的事件，因为它们分布在只有两种异常的肿瘤中。
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. in contrast to many other hematological malignancies, no chromosomal abnormalities with a diagnostic or prognostic value have been identified in DLBCL. Numerical chromosomal imbalances were characterized by comparative genomic hybridization (CGH) performed on 54 DLBCL tumors from a total of 40 patients. The clonal relatedness was demonstrated in 9 of 11 pairs of matched diagnostic tumors and their relapses as determined by IGH gene rearrangement analysis and/or the CGH profiles. Furthermore, immunohistochemical expression analyses of BCL2 and BCL6/LAZ3 were performed on all cases. Copy number changes were detected in 94% of the diagnostic tumor samples and in all of the relapses. Chromosomal losses in diagnostic tumors were preferentially observed at 8p22-pter (29%), 1p34-pter (26%), 6q23-qter (20%), 17p12-pter (17%) and 22q (17%),9p23-pter (14%), whereas gains were mainly seen in Xq25-26 (43%), 13q22 (26%), 12cen-q14 (20%), 3q24-25 (11%), 7 (11%), and 18q12-21 (11%). Loss of 22q was significantly more commonly seen in the diagnostic tumor samples with more advanced clinical stage in other words, Stage III-IV compared with Stage I-II, and band 18q21 was significantly more often gained in relapses as compared to diagnostic tumors. None of the recurrent alterations were detected as a single abnormality, suggesting that other genetic lesions below the detection level of CGH may be the initiating event in the tumorigenesis of DLBCL. However, the distribution of CGH alterations support the idea of a progression of genetic events where loss of 8p and 9p and gain of 3q, 13q, and 18q would represent relatively early events because they were distributed in tumors with only two abnormalities.