Genetic instability is associated with histological transformation of follicle center lymphoma
Genetic instability is associated with histological transformation of follicle center lymphoma
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DOI：
10.1038/sj.leu.2401978
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发表时间：
2000-12-01
期刊：
影响因子：
11.4
通讯作者：
Matolcsy, A
中科院分区：
文献类型：
--
作者：
Nagy, M;Balázs, M;Matolcsy, A
滤泡中心淋巴瘤（FCL）是一种惰性B细胞非霍奇金淋巴瘤（NHL），其遗传特征为t（14;18）易位。FCL的组织学转化和临床进展通常与核酸和染色体水平的继发性遗传改变相关。为了确定FCL组织学转化中发生的基因组不稳定性的类型和模式以及DNA错配修复缺陷在此过程中的作用，我们对FCL转化为弥漫性大细胞淋巴瘤（DLCL）患者的系列活检标本进行了微卫星分析、比较基因组杂交（CGH）和hMLH 1和hMSH 2基因突变分析。对8例患者的配对活检样本进行了分析，微卫星不稳定性和结构改变的hMLH 1和hMSH 2基因，和5例患者的肿瘤样本进行CGH分析。高水平的微卫星不稳定性与两例FCL的组织学转化相关，但在任何淋巴瘤样本中均未检测到hMLH 1和hMSH 2基因突变。在进行CGH分析的五个病例中，FCL的组织学转化与21个染色体区域的基因组不平衡相关。所发现的基因组异常是相当异质性的，并且在转化的DLCL中没有过度表达的遗传变化。这些数据表明，FCL向DLCL的组织学转化通常与核酸和染色体水平的全基因组不稳定性相关，尽管hMSH 1和hMLH 2基因的突变不参与该过程。
Follicle center lymphoma (FCL) is an indolent B cell non-Hodgkin's lymphoma (NHL) characterized genetically by the t(14;18) translocation. Histological transformation and clinical progression of FCLs are frequently associated with secondary genetic alterations at both nucleic acid and chromosomal levels. To determine the type and pattern of genomic instability occurring in histological transformation of FCLs and the role of DNA mismatch repair defects in this procedure, we have performed microsatellite analysis, comparative genomic hybridization (CGH) and mutational analysis of hMLH1 and hMSH2 genes on serial biopsy specimens from patients with FCL transformed to diffuse large cell lymphoma (DLCL). Paired biopsy samples of eight patients were analyzed for microsatellite instability and structural alterations for hMLH1 and hMSH2 genes, and tumor samples of five patients were subjected to CGH analysis. A high level of microsatellite instability was associated with histological transformation of two cases of FCL, but no mutations of the hMLH1 and hMSH2 genes were detected in any of the lymphoma samples. In the five cases subjected to CGH analysis, the histological transformation of FCLs was associated with genomic imbalances at 21 chromosomal regions. The genomic abnormalities found were rather heterogeneous and none of the genetic changes were overrepresented in the transformed DLCLs. These data suggest that histological transformation of FCLs to DLCL is frequently associated with genome wide instability at both nucleic acid and chromosomal levels, although mutations of the hMSH1 and hMLH2 genes are not involved in this process.