原发性纵隔大B细胞淋巴瘤和弥漫性大B细胞淋巴瘤具有相似的基因组改变模式。

Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma.

作者信息

Palanisamy Nallasivam, Abou-Elella Ashraf A, Chaganti Seeta R, Houldsworth Jane, Offit Kenneth, Louie Diane C, Terayu-Feldstein Julie, Cigudosa Juan C, Rao Pulivarthi H, Sanger Warren G, Weisenburger Dennis D, Chaganti R S K

机构信息

Laboratory of Cancer Genetics, Cell Biology Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

出版信息

Genes Chromosomes Cancer. 2002 Feb;33(2):114-22. doi: 10.1002/gcc.10016.

DOI:10.1002/gcc.10016

PMID:11793437

Abstract

To address the possible genetic relationship between primary mediastinal large-B-cell lymphoma (PMLBCL) and diffuse large-B-cell lymphoma (DLBCL), we compared DNA copy number changes identified by comparative genomic hybridization (CGH) analysis of 40 PMLBCL and 91 DLBCL tumors. We assessed their karyotypes by G-banding; amplification of MYC, BCL2, and REL genes by Southern blotting; and incidence of nonpolymorphic BCL6 mutations by single-strand conformation polymorphism analysis (SSCP). Overall, CGH identified overlapping and nonoverlapping patterns of DNA copy number changes in the two groups. Among the latter changes, gains of chromosomes 8, 11, 15, and 16 and losses of chromosomes 5, 10, 15, 16, 17, and 20 were seen only in DLBCL, and gains of chromosomes 10, 21, and 22 and losses of chromosomes 11, 13, and 18 were seen only in PMLBCL. Several overlapping changes were identified in both groups, with variation in incidence. Statistical analysis of these changes showed significant gains of chromosomes 3 (P <or= 0.05) and 7q (P <or= 0.05) in DLBCL and gains of chromosomes 9 (P <or= 0.05) and 19 (P <or= 0.05) and the X chromosome (P <or= 0.05) and loss of chromosome 4 (P <or= 0.05) in PMLBCL. Frequent recurring DNA amplification at 2p13-15 and less frequent amplification at 6p21, 12q13, and 18q21 were noted in both groups. Recurring amplification at 1q21 was seen only in DLBCL, whereas nonrecurring amplification at 10p11.2 and 15q22-24 was seen only in PMLBCL. G-banded karyotype analysis identified t(3;14)(q27;q32) in one and t(14;18)(q32;q21) in two cases of PMLBCL. Seven of 13 cases exhibited SSCP variants in the 5' noncoding region of BCL6. In addition, 19 of 24 PMLBCLs assayed for BCL6 protein expression by immunohistochemistry showed positive results, indicating an origin from a germinal center (GC)-derived B cell. Based on these data, we conclude that PMLBCL is a distinct entity among GC-derived high-grade DLBCLs.

摘要

为了探讨原发性纵隔大B细胞淋巴瘤（PMLBCL）与弥漫性大B细胞淋巴瘤（DLBCL）之间可能存在的遗传关系，我们比较了40例PMLBCL肿瘤和91例DLBCL肿瘤经比较基因组杂交（CGH）分析确定的DNA拷贝数变化。我们通过G显带评估其核型；通过Southern印迹分析MYC、BCL2和REL基因的扩增情况；通过单链构象多态性分析（SSCP）检测非多态性BCL6突变的发生率。总体而言，CGH确定了两组中DNA拷贝数变化的重叠和非重叠模式。在后者的变化中，8号、11号、15号和16号染色体的增加以及5号、10号、15号、16号、17号和20号染色体的缺失仅在DLBCL中出现，而10号、21号和22号染色体的增加以及11号、13号和18号染色体的缺失仅在PMLBCL中出现。两组中均发现了一些重叠变化，但发生率有所不同。对这些变化的统计分析显示，DLBCL中3号染色体（P≤0.05）和7q（P≤0.05）有显著增加，PMLBCL中9号染色体（P≤0.05）、19号染色体（P≤0.05）和X染色体（P≤0.05）有增加，4号染色体有缺失（P≤0.05）。两组均发现2p13 - 15处频繁出现反复性DNA扩增，6p21、12q13和18q21处扩增频率较低。1q21处的反复性扩增仅在DLBCL中出现，而10p11.2和15q22 - 24处的非反复性扩增仅在PMLBCL中出现。G显带核型分析在1例PMLBCL中发现t(3;14)(q27;q32)，在2例中发现t(14;18)(q32;q21)。13例中有7例在BCL6的5'非编码区出现SSCP变异。此外，通过免疫组织化学检测BCL6蛋白表达的24例PMLBCL中有19例呈阳性结果，表明其起源于生发中心（GC）来源的B细胞。基于这些数据，我们得出结论，PMLBCL是GC来源的高级别DLBCL中的一个独特实体。