TEMPORAL CHANGES IN MURINE GENOMIC EXPRESSION PATTERN DELINEATED BY MR

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。肿瘤的基因表达谱随时间进展和空间分布而变化。在本研究中，对比增强MRI用于非侵入性表征实体瘤，描绘肿瘤进展的空间异质性和时间变化，并指导组织采样进行基因组分析。在肿瘤进展的不同阶段，基因的表达水平可以作为诊断和治疗的潜在靶点。方法与讨论：采用GE临床1.5T MR自旋回波（t1加权）和快速自旋回波（t2加权）脉冲序列对C3H/K小鼠进行VII型鳞状细胞癌成像。肿瘤植入后2周开始注射造影剂（Gd(DTPA)）前后的图像。肿瘤在T1和T2-wt图像上表现出不同的造影剂摄取和不同的空间和时间成像模式。根据T1和T2-wt MRI特征的变化定义三个不同的分期。收集1期肿瘤的边缘和中心区域，以及2期和3期肿瘤的对比增强和非增强区域进行H&E染色和基因组学研究。对(1)边缘/CE区和(2)中心/NE区3个阶段进行两组比较，获得具有统计学意义变化的基因。通过比较边缘/CE区和中心/NE区三个阶段表达水平差异（折叠变化）大于约2的基因可分为6个不同的功能类别。在两个比较中，共有5个基因发生了显著变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Gene expression profiles in tumors vary with temporal progression and spatial distribution. In this study, contrast-enhanced MRI was used to non-invasively characterize solid tumors, to delineate the spatial heterogeneity and temporal changes of tumor progression, and to guide tissue sampling for genomic analysis. Genes identified with expression level among different stages of tumor progression can be potential targets for diagnostics and therapeutics. Methods and Discussion: C3H/K mice bearing squamous cell carcinoma VII were imaged with GE clinical 1.5T MR using spin-echo (T1-weighted) and fast spin echo (T2-weighted) pulse sequence. Images were obtained pre- and post-contrast agent (Gd(DTPA)) injection starting 2 weeks after tumor implantation. Tumors show differential contrast uptake and distinct imaging patterns in T1 and T2-wt images spatially and temporally. Three different stages were defined based on changes in the T1- and T2-wt MRI features. Rim and center regions from Stage 1 tumors, and regions with contrast enhancing and non-enhancing from Stage 2 and 3 tumors were collected for H&E staining and genomic study. Two sets of comparison for (1) rim/CE and (2) center/NE regions across the 3 stages were conducted to obtain genes with statistically significant changes. Genes from comparisons for rim/CE and center/NE regions with differential expression level (fold change) among the three stages to be larger than approximately 2 fall into 6 different function categories. Total of 5 genes have significant changes on both comparisons.