Chromosomal and gene amplification in diffuse large B-cell lymphoma
Chromosomal and gene amplification in diffuse large B-cell lymphoma
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DOI：
10.1182/blood.v92.1.234.413k22_234_240
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发表时间：
1998-07-01
期刊：
影响因子：
20.3
通讯作者：
Chaganti, RSK
中科院分区：
文献类型：
--
作者：
Rao, PH;Houldsworth, J;Chaganti, RSK
导致特定癌基因失调的染色体易位是约 50% 弥漫性大 B 细胞淋巴瘤 (DLBL) 病例的特征。为了描述可能对描述 DLBL 临床特征有价值的其他遗传特征，我们研究了在纪念斯隆-凯特琳癌症中心 (MSKCC) 连续确定的 96 例诊断病例的基因扩增发生率，这是一种先前被证明与肿瘤进展和临床结果相关的遗传异常。对 20 个病例的子集进行了比较基因组杂交 (CGH) 分析，确定了 9 个染色体扩增位点（1q21-23、2p12-16、8q24、9q34、12q12-14、13q32、16p12、18q21-22 和 22q123）。选择映射到这些位点的候选扩增基因进行进一步分析基于它们在淋巴样细胞和淋巴瘤发展中的已知作用和/或肿瘤中的扩增历史，对满足这些标准的 6 个基因（REL (2p12-16)、MYC (8q24)、BCL2 (18q21)、GLI、CDK4 和 MDM2 (12q13-14)）进行了对 96 个 DLBL DNA 的定量 Southern 印迹分析。基因扩增（四个或更多拷贝）的发生率范围为 11% 至 23%，该分析与我们之前的发现一致，即 REL 扩增与结外表达相关。此外，BCL2 重排和/或 REL、MYC、BCL2、CDK4 和 MDM2 扩增与晚期疾病相关。这些数据首次表明，染色体区域和基因的扩增是 DLBL 中的常见现象，并证明了其潜在意义。 (C) 1998 年美国血液学会。
Chromosomal translocations leading to deregulation of specific oncogenes characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL). To characterize additional genetic features that may be of value in delineating the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC) for incidence of gene amplification, a genetic abnormality previously shown to be associated with tumor progression and clinical outcome. A subset of 20 cases was subjected to comparative genomic hybridization (CGH) analysis, which identified nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14, 13q32, 16p12 18q21-22, and 22q123. Candidate amplified genes mapped to these sites were selected for further analysis based on their known roles in lymphoid cell and lymphoma development, and/or history of amplifica tion in tumors. Probes for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2 (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or more copies) with incidence ranging from 11% to 23%. This analysis is consistent with our previous finding that REL amplification is associated with extranodal presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4, and MDM2 amplification was associated with advanced stage disease. These data show, for the first time, that amplification of chromosomal regions and genes is a frequent phenomenon in DLBL and demonstrates their potential significance in lymphomagenesis. (C) 1998 by The American Society of Hematology.