Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations
Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations
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DOI：
10.1182/blood-2002-07-2119
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发表时间：
2003-04-15
期刊：
影响因子：
20.3
通讯作者：
Lossos, IS
中科院分区：
文献类型：
--
作者：
Martinez-Climent, JA;Alizadeh, AA;Lossos, IS
应用基因组芯片比较杂交技术（CGH）检测了一系列原发于滤泡中心淋巴瘤（FCL）并随后转化为弥漫性大B细胞淋巴瘤（DLBCL）患者的配对活检标本的基因组畸变。这些畸变对基因表达的后果进行了测定，通过比较与这些标本使用cbNA微阵列的表达分析。在转化后观察到获得性基因组异常的异质性模式，其中一些在小的患者亚群中复发。一些在转化时获得的基因组畸变，如1 q21-q24的增加/扩增，2 p16（REL/BCL 11 A基因座）、3qV-q29（包括BCL 6基因座）、7q11.2-q22.1、12 pter-q12、18 q21（包括BCL 2基因座）和Xq以及6 q22-q24、13 q14-q21和17 p13（P53基因座）的缺失与FCL/DLBCL发病机制有关。16此外，还发现了先前未报道的与FCL转化相关的新型基因组失衡，如4p 12-pter、5 p12-p15、6p12.3-p21、9 p23、9 q13 q31、16 q、17 q21的过度表达，以及1p36.3、4021-q23、5 q21-q23、9 q31-qter、11 q24-q25和15 q23的缺失。我们观察到许多基因的差异表达谱的区域内的增益和删除转化后，包括新的靶基因与FCL转化。然而，其他基因并没有表现出失调的表达，尽管他们的位置在这些领域。总之，阵列CGH和表达分析的组合提供了FCL向DLBCL转化的更全面的画面。该过程与获得可变谱的基因组不平衡相关，所述基因组不平衡影响在转化时靶向的含有过表达或低表达基因的复发性染色体区域。(C)2003年，美国血液学会。
Genomic aberrations in a series of paired biopsy samples from patients who presented initially with follicle center lymphoma (FCL) and subsequently transformed to diffuse large B-cell lymphoma (DLBCL) were measured by array comparitive genomic hybridization (CGH). The consequences of these aberrations on gene expression were determined by comparison with expression analysis on these specimens using cbNA microarrays. A heterogeneous pattern of acquired genomic abnormalities was observed upon transformation, some of which Were recurrent in small subsets of patients. Some, of the genomic aberration acquired upon transformation, such as gain/amplification of 1q21-q24., 2p16 (REL/BCL11A gene loci), 3qV-q29 (including the BCL6 locus), 7q11.2-q22.1 12pter-q12, 18q21 (including the BCL2 locus) and Xq, and deletion of 6q22-q24, 13q14-q21 and 17p13 (P53 locus) have been previously implicated in the FCL/DLBCL pathogenesis. 16 addition, novel genomic imbalances not previously reported in association with FCL transformation, such as overrepresentation of 4p12-pter, 5p12-p15, 6p12.3-p21, 9p23,9q13 q31,16q, 17q21, and loss of 1p36.3, 4021-q23, 5q21-q23, 9q31-qter, 11q24-q25, and 15q23, were identified. We observed a differential expression profile of many genes within regions of gain and deletion upon transformation, including novel target genes associated with FCL transformation. However, other genes did not show deregulated expression despite their location within these areas. In summary, the combination of array CGH and expression analysis provides a more comprehensive picture of the transformation of FCL to DLBCL. This process is associated with the acquisition of a variable spectrum of genomic imbalances affecting recurrent chromosomal areas that harbor overexpressed or underexpressed genes targeted upon transformation. (C) 2003 by The American Society of Hematology.