TEMPORAL CHANGES IN MURINE GENOMIC EXPRESSION PATTERN DELINEATED BY MR

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。前言：肿瘤中的基因表达谱随时间进展和空间分布而变化。在这项研究中，增强MRI被用来非侵入性地描述实体瘤的特征，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中发现的表达水平的基因可能成为诊断和治疗的潜在靶点。方法与讨论：用自旋回波(T1加权)和快速自旋回波(T2加权)脉冲序列对C3H/K小鼠进行GE临床期1.5T磁共振成像。于肿瘤种植后2周开始注射造影剂(Gd(DTPA))。肿瘤在T1和T2-wt图像上表现出不同的对比度摄取和不同的成像模式。根据T1和T2加权成像特征的变化，将其分为三个不同的阶段。收集1期肿瘤的边缘和中心区，2期和3期肿瘤的增强和非增强区域，进行HE染色和基因组学研究。对3个阶段的(1)RIM/CE和(2)CENTER/NE区域进行两组比较，以获得具有统计学意义变化的基因。比较3个阶段差异表达水平(倍数变化)大于2的边缘/CE和中心/NE区域的基因，可分为6个不同的功能类别。在两次比较中，共有5个基因发生显著变化。

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.