用比较基因组杂交技术研究弥漫大B细胞淋巴瘤分子细胞遗传学异常及其意义

Molecular cytogenetic aberration analyzed by comparative genetic hybridization and its signification in diffuse large-B cell lymphoma

背景与目的:弥漫大B细胞淋巴瘤(DLBCL)是非霍杰金淋巴瘤(NHL)中最常见的一种类型,发病机制较为复杂,且预后较差。为了从基因组水平全面理解DLBCL的分子异常,本研究采用比较基因组杂交技术(CGH)研究DLBCL的分子细胞遗传学异常,探讨DLBCL的分子细胞遗传学异常与临床特征的相关性。方法:采用CGH技术对24例DLBCL患者的全基因组遗传物质的扩增/缺失进行检测,分析CGH检测结果与DLBCL的临床特征及生存期的相关性。结果:24例DLBCL中62.5%病例发生染色体水平的扩增/缺失,20.8%病例发生累及6q的缺失,16.7%病例发生累及18q扩增;CGH检测异常组与正常组比较:CGH异常组患者Ann arbor分期多为Ⅲ/Ⅳ期,出现全身症状的机率较高,治疗疗效较差,生存期较短,但2组结外累及发生机率差异无显著性。结论:基因组水平发生的遗传物质扩增/缺失是DLBCL常见的分子细胞遗传学异常;6q15-21缺失和18q11-ter扩增是DLBCL非随机分子细胞遗传学异常;CGH检测异常是DLBCL不良临床过程和预后标志。

Background and Purpose： Diffuse large-B-eell lymphoma（ DLBCL）. the most common type of NHL, has various molecular defects and poor prognosis. The purposes of this paper are to understand the molecular pathogenesis of DLBCL at whole genome level and to identify genetic alteration in diffuse large-B cell lymphoma in humans and to analyze the correlation between the genetic aberration and the elinic characteristics. Methods： Using comparative genomic hybridization to investigate the genomic changes in 24 cases of diffuse large-B cell lymphoma and to analyze the relationship between these aberrations and clinical parameters including Ann arbor stage, systemic symptoms, chemotherapy efficacy and survival. Results： Aberration was detected in 62.5% of 24 cases; the most common chromosomal alterations included loss of 6q15-21 as well as gain of 18q11-ter, their incidences were 20.8% and 16.7% , respectively. Comparison between the group of patients with normal and abnormal CGH showed that more often in stage Ⅲ/Ⅳ, the higher incidence of systemic symptoms, poor chemotherapy efficacy and survival were deteeted in the group of patients with abnormal CGH （P 〈 0.05）, but there was no difference in the incidence of extranodal involvement between the two groups. Conclusions： The gains and / or losses occurring in genomic DNA are the commom molecular cytogenetic aberrations in DLBCL patients; loss of 6q15-21 and gain of 18q11-ter is nonrandom molecular cytogenetie aberration in DLBCL patients; abnormal CGH is a sign of highly malignant course of disease and poor survival in DLBCL patients