Clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-Cell lymphomas
Clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-Cell lymphomas
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DOI：
10.1200/jco.2004.11.025
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发表时间：
2004-09-01
影响因子：
45.3
通讯作者：
Campo, E
中科院分区：
文献类型：
--
作者：
Beà, S;Colomo, L;Campo, E
目的探讨弥漫性大B细胞淋巴瘤（DLBCL）中染色体不平衡的临床病理意义和预后价值。患者和方法我们采用比较基因组杂交和实时定量聚合酶链反应（PCR）、单链构象多态性、结果18 q（20%）、Xq（15%）、2 p、7 q、和12 p（14%），以及6 q和17 p的丢失（14%）。在2 p13-p16和18 q21位点检测到频繁的高水平DNA扩增。实时定量PCR检测REL和BCL 11 A基因扩增的9例患者与增益在2 p13-p16和只有在一个额外的患者与正常的2号染色体。BCL-2基因在12例18 q21扩增的肿瘤中扩增，而在39例18 q21扩增正常的肿瘤中无一例扩增。p53基因失活在9/58（16%）的肿瘤中检测到，通常与17 p丢失有关。18 q增加的肿瘤与大量染色体不平衡、原发淋巴结转移、高血清乳酸脱氢酶水平、高国际预后指数、较短的病因特异性生存期和高复发风险显著相关。17 p和p53基因改变的损失与没有完全响应achievement.ConclusionThese结果表明，DLBCL有一个特征性的模式的基因组改变; 18 q增益或扩增和17 p损失与特定的临床病理特征和侵略性的临床行为。需要更多的研究来证实这些观察结果在更大的患者系列。(C)2004年，美国临床肿瘤学会。
PurposeTo determine the clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-cell lymphomas (DLBCL).Patients and MethodsWe have examined 64 tumors at diagnosis using comparative genomic hybridization and real-time quantitative polymerase chain reaction (PCR), single-stranded conformational polymorphism, and DNA sequencing for the analysis of several potential target genes.ResultsThe most recurrent alterations were gains of 18q (20%), Xq (15%), 2p, 7q, and 12p (14%), and losses of 6q and 17p (14%). Frequent high-level DNA amplifications were detected at 2p13-p16 and 18q21 loci. Real-time quantitative PCR detected REL and BCL11A gene amplifications in the nine patients with gains at 2p13-p16 and only in one additional patient with normal chromosome 2. Similarly, the BCL-2 gene was amplified in the 12 tumors with gains of 18q21 but in none of 39 patients with normal 18q profile. p53 gene inactivation was detected in nine of 58 (16%) tumors and was commonly associated with 17p losses. Tumors with 18q gains were significantly associated with a high number of chromosomal imbalances, primary nodal presentation, high serum lactate dehydrogenase levels, high International Prognostic Index, shorter cause-specific survival, and a high risk of relapse. Losses of 17p and p53 gene alterations were associated with an absence of complete response achievement.ConclusionThese results suggest that DLBCLs have a characteristic pattern of genomic alterations; 18q gains or amplifications and 17p losses are associated with particular clinicopathological features and aggressive clinical behavior. Additional studies are needed to confirm these observations in larger series of patients. (C) 2004 by American Society of Clinical Oncology.