Kang Hyun-Mi, Jang Ja-June, Langford Cordelia, Shin Seung-Hun, Park Seon-Yang, Chung Yeun-Jun
Department of Microbiology, College of Medicine, Catholic University of Korea, Socho-gu, Seoul 137-701, Republic of Korea.
Cancer Genet Cytogenet. 2006 Apr 1;166(1):27-35. doi: 10.1016/j.cancergencyto.2005.08.002.
The genetic mechanism for the development and progression of a lymphoma is unclear. This study investigated the alterations in the DNA copy number and the expression profiles of the genes located in the altered regions in mouse thymic lymphomas that were induced by two mutagens, gamma-irradiation and N-methyl-N-nitrosourea (MNU). Microarray-based comparative genomic hybridization was used to precisely delineate the boundaries of the altered region. The copy number gains of chromosomes 4 and 5 were observed only in the radiation-induced lymphomas, and gains of chromosomes 10 and 14 were observed only in the MNU-induced lymphomas. Regional copy number losses in chromosomes 11, 16, and 19 appeared frequently in the radiation-induced lymphomas. The cancer-related genes Pten, Ikaros/Znfn1a1, Ercc4, and Top3b were located in the minimal deletion regions. In particular, the expression levels of the Pten, Top3b, and Ikaros genes were downregulated in both lymphoma groups, but the expression level of Ercc4 was downregulated only in the MNU group. This study also examined the expression levels of Sparc, Cxcl1, and Myc (synonym: c-Myc), which are located in the copy number gained chromosomes. Sparc was upregulated specifically in the radiation group, and Cxcl1 in the MNU group. c-Myc was upregulated in both groups. There was limited correlation between the DNA copy number profiles and the expression of the cancer-related genes in mouse lymphomagenesis. The chromosome aberrations and novel expression profiles of the cancer-related genes within the altered regions may provide important clues to the genetic mechanism for the development of lymphoma.
淋巴瘤发生发展的遗传机制尚不清楚。本研究调查了由两种诱变剂γ射线和N-甲基-N-亚硝基脲（MNU）诱导的小鼠胸腺淋巴瘤中DNA拷贝数的变化以及位于改变区域的基因的表达谱。基于微阵列的比较基因组杂交用于精确划定改变区域的边界。仅在辐射诱导的淋巴瘤中观察到4号和5号染色体的拷贝数增加，仅在MNU诱导的淋巴瘤中观察到10号和14号染色体的增加。11号、16号和19号染色体的区域拷贝数缺失在辐射诱导的淋巴瘤中频繁出现。癌症相关基因Pten、Ikaros/Znfn1a1、Ercc4和Top3b位于最小缺失区域。特别是，Pten、Top3b和Ikaros基因的表达水平在两个淋巴瘤组中均下调，但Ercc4的表达水平仅在MNU组中下调。本研究还检测了位于拷贝数增加染色体上的Sparc、Cxcl1和Myc（同义词：c-Myc）的表达水平。Sparc仅在辐射组中特异性上调，Cxcl1在MNU组中上调。c-Myc在两组中均上调。在小鼠淋巴瘤发生过程中，DNA拷贝数谱与癌症相关基因的表达之间的相关性有限。改变区域内的染色体畸变和癌症相关基因的新表达谱可能为淋巴瘤发生发展的遗传机制提供重要线索。
