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遗传背景对肿瘤细胞基因组构成的影响。

The impact of the genetic background on the genome make-up of tumor cells.

机构信息

Systems Biology Research Centre-Tumor Biology, School of Life Sciences, University of Skövde, Skövde, Sweden.

出版信息

Genes Chromosomes Cancer. 2012 May;51(5):438-46. doi: 10.1002/gcc.21929. Epub 2012 Jan 17.

Abstract

Endometrial adenocarcinoma (EAC) is the most common form of malignancy in the female genital tract, ranking as the fourth leading form of invasive tumors that affect women. The BDII inbred rat strain has been used as a powerful tumor model in studies of the genetic background of EAC. Females from the BDII strain are prone to develop tumors with an incidence of more than 90%. Development of EAC in BDII female rats has similarities in pathogenesis, histopathological, and molecular properties to that of human, and thus represents a unique model for analysis of EAC tumorigenesis and for comparative studies in human EACs. In a previous study, a set of rat EAC cell lines derived from tumors developed in female crossprogenies between BDII and nonsusceptible rat strains were analyzed by spectral karyotyping (SKY). Here we present an analysis with specific focus on the impact of different genetic backgrounds on the rate and occurrence of genetic aberrations in experimental tumors using data presented in the previous report. We could reveal that the ploidy state, and the abundance and type of structural as well as numerical change differed between the two genetic setups. We have also identified chromosomes harboring aberrations independent of genetic input from the nonsusceptible strains, which provide valuable information for the identification of the genes involved in the development of EAC in the BDII model as well as in human endometrial tumors.

摘要

子宫内膜腺癌(EAC)是女性生殖道最常见的恶性肿瘤,是第四种常见的侵袭性女性肿瘤。BDII 近交系大鼠已被广泛用于 EAC 遗传背景的研究中。BDII 大鼠的雌性个体易患肿瘤,发病率超过 90%。BDII 雌性大鼠的 EAC 发生发展与人类具有相似的发病机制、组织病理学和分子特征,因此代表了分析 EAC 肿瘤发生和人类 EAC 比较研究的独特模型。在之前的一项研究中,对来源于 BDII 与非易感大鼠杂交雌性个体肿瘤的一组大鼠 EAC 细胞系进行了光谱核型分析(SKY)。在这里,我们使用之前报道中的数据,专门分析了不同遗传背景对实验性肿瘤中遗传异常的发生和发生率的影响。我们发现,在两种遗传背景下,细胞的倍性状态以及结构和数量变化的丰富度和类型均存在差异。我们还鉴定出了不受非易感株遗传输入影响的染色体,这些染色体的畸变为鉴定 BDII 模型中 EAC 发生发展以及人类子宫内膜肿瘤中涉及的基因提供了有价值的信息。

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