Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model.
Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model.
复制标题
小鼠 cDNA 微阵列的比较基因组杂交及其在小鼠淋巴瘤模型中的应用。
DOI：
10.1038/sj.onc.1208751
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Pollack,JonathanR
中科院分区：
文献类型：
--
作者：
Sander,Sandrine;Bullinger,Lars;Karlsson,Asa;Giuriato,Sylvie;Hernandez-Boussard,Tina;Felsher,DeanW;Pollack,JonathanR
基于微阵列的格式提供了一种高分辨率的替代传统的，基于染色体的比较基因组杂交（CGH）方法，用于评估人类癌症中的DNA拷贝数改变（CNA）全基因组。对于小鼠肿瘤，阵列CGH应该提供更大的优势，因为小鼠染色体更难以单独辨别。我们在这里报告的适应和评估的cDNA微阵列为基础的CGH方法的常规表征CNA在小鼠肿瘤中，使用小鼠cDNA微阵列代表14000个不同的基因，从而提供了一个平均映射分辨率为109 kb。作为第一个应用程序，我们的特点是CNA在一组10个原发性和复发性淋巴瘤来自Myc诱导的小鼠淋巴瘤模型。在原发性淋巴瘤和更常见的Myc非依赖性复发中，我们鉴定了染色体3G 3 - 3 H4处的复发性基因组DNA丢失和染色体3F 2处的复发性扩增。1- 3G 3和染色体15 E1/E2- 15 F3的边界，我们确定了高分辨率。此外，通过使用相同的微阵列平台分析基因表达，我们在CNA中鉴定了表现出突变表达的候选癌症基因的相关子集，包括Mcl 1（髓样细胞白血病序列1），一种位于chr 3扩增子峰内的高表达抗凋亡基因。因此，小鼠cDNA微阵列上的CGH代表了用于小鼠肿瘤中CNA的高分辨率表征的可靠方法，以及用于阐明小鼠模型中肿瘤发展和进展中的分子事件的有力方法。
Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing∼ 14 000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3–3H4, and recurrent amplifications at chromosome 3F2. 1–3G3 and chromosome 15E1/E2–15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models.