摘要目的 利用阵列比较基因组杂交(aCGH)技术探讨间变性大细胞淋巴瘤(ALCL)的分子遗传学异常.方法 采用免疫组织化学EnVision法及荧光原位杂交技术对25例ALCL进行间变性淋巴瘤激酶(ALK)蛋白及基因分子遗传学异常的检测；利用aCGH技术进行全基因组遗传学检测,并对检测结果与ALCL的ALK蛋白表达进行相关性分析.结果 25例ALCL中均有染色体片段的扩增/缺失,且扩增多于缺失.其中＞50％病例中存在染色体区域5p13.2、3q1.1、2q21.3、3p25.1、14q32.33、17q21.2的获得；30％ ～ 50％病例中存在染色体区域4q27、6p22.1、20p11.21、2q22.3、4q35.1、1p36.22、8p23.1、8p12、11q14.1、12q13.13、19p13.3的获得；36.0％ (9/25)及24.0％ (6/25)的ALCL病例中存在3q26.1及3q26.31染色体区域的缺失.染色体区域2q21.3、6p22.1及3p25.1的获得在ALK阳性与ALK阴性ALCL病例中差异有统计学意义(P＜0.05).结论 ALCL存在着较为复杂的分子遗传学变化,即遗传学不平衡性.其中,染色体片段的扩增多于缺失.位于2q21.3、6p22.1及3p25.1的遗传学不平衡在ALK阳性和ALK阴性ALCL之间存在显著差异,表明ALK阳性和阴性ALCL所涉及的遗传学异常不同,可能涉及不同的信号转导通路.

abstractsObjective To use array-based comparative genomic hybridization (aCGH) technology to study the molecular cytogenetic abnormalities of anaplastic large cell lymphoma (ALCL) at genome level.Methods ALK protein expression and molecular genetic abnormalities were detected by immunohistochemistry and fluorescence in situ hybridization,respectively,in 25 cases of ALCL.Any chromosomal gains/losses were detected by aCGH and correlated with ALK status.Results aCGH showed that chromosomal alterations in all 25 ALCL cases,and the frequency of chromosomal gains was higher than that of the losses.Chromosomal gains at 5p13.2,3q21.1,2q21.3,3p25.1,14q32.33,and 17q21.2 regions were detected in more than 50％ of the ALCL cases; gains at 4q27,6p22.1,20p1 1.21,2q22.3,4q35.1,1p36.22,8p23.1,8p12,11q14.1,12q13.13,and 19p13.3 regions were detected in 30％-50％ of the ALCL cases; chromosomal losses at 3q26.1 and 3q26.31 regions were detected in 36.0％ (9/25)and 24.0％ (6/25)of the ALCL cases,respectively.Chromosomal gains at 2q21.3,6p22.1 and 3p25.1 regions showed significant differences between ALK (+) and ALK (-) ALCL groups (P ＜ 0.05).Conclusions aCGH demonstrates complex molecular genetic variations in all ALCL cases.Gains at 2q21.3,6p22.1 and 3p25.1 regions are significantly different between ALK (+) and ALK (-) ALCL groups,suggesting that the pathogenesis of ALK (+) and ALK (-) ALCL may involve different signaling pathway.