Phenotype and Gene Expression in Odontogenic Tumors

牙源性肿瘤的表型和基因表达

• 批准号: 7038429
• 负责人: John T. Wright
• 金额: $ 31.21万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7038429
• 关键词: clinical research; gene expression; genes; human; mouth neoplasms; neoplasm /cancer; phenotype

DESCRIPTION (provided by applicant): Unraveling the human genome has lead to rapid advances in our knowledge of the molecular genetic controls that regulate and determine both normal and pathological tissue development. While progress has been rapid and substantial in the areas of simple hereditary conditions, far less has been learned of complex conditions including the molecular events leading to and driving tumorigenesis. The development of molecular biological techniques that allow analysis of large numbers of genes simultaneously now makes it possible to effectively and efficiently evaluate gene expression between different tissues and/or neoplasms. These powerful molecular techniques allow novel experimentation into the relationship between the phenotype and genotype of both normal and pathological tissues. Previous studies show overexpression of and/or mutation of RAS genes in odontogenic tumors and the genesis of tumors in locations where stem cells are localized. We hypothesize that the heterogeneous odontogenic tumor phenotypes result from differential expression of multiple genes that are downstream of the RAS and/or WNT pathways. We propose to test this hypotheses by ascertaining odontogenic tumors from humans having phenotypically diverse lesions including ameloblastomas, odontomas, odontogenic keratocysts and less common tumor types. Detailed phenotype profiles will be determined on all tumors using clinical, histological, and imaging techniques. Characterization of differential gene expression between tumors will be accomplished using cDNA microarrays printed to evaluate 16,000 mouse or human genes. Differential gene expression of specific cell populations within tumors will be evaluated using Laser Capture Microscopy and microarrays. RAS and p53 genes will be sequenced for mutations to discover molecular initiators of tumorigenesis. Microarray data is analyzed using state of the art bioinformatics to identify over and underexpressed genes compared with a commercially available reference RNA that allows standardization between laboratories conducting similar research. Gene data will be placed on our web site in a timely fashion for data sharing. These studies will provide the first detailed mutational and gene profile studies of human odontogenic tumors.

描述（由申请人提供）：解开人类基因组导致我们对调节和决定正常和病理组织发育的分子遗传控制的认识迅速进步。虽然在简单的遗传性疾病领域取得了快速而实质性的进展，但对复杂疾病（包括导致和驱动肿瘤发生的分子事件）的了解却少之又少。允许同时分析大量基因的分子生物学技术的发展现在使得有效且高效地评估不同组织和/或肿瘤之间的基因表达成为可能。这些强大的分子技术允许对正常组织和病理组织的表型和基因型之间的关系进行新的实验。先前的研究表明，牙源性肿瘤中 RAS 基因过度表达和/或突变，以及肿瘤在干细胞定位的部位发生。我们假设异质性牙源性肿瘤表型是由 RAS 和/或 WNT 通路下游多个基因的差异表达造成的。我们建议通过确定人类的牙源性肿瘤来检验这一假设，这些肿瘤具有表型多样的病变，包括成釉细胞瘤、牙瘤、牙源性角化囊肿和不太常见的肿瘤类型。将使用临床、组织学和成像技术确定所有肿瘤的详细表型特征。肿瘤之间差异基因表达的表征将使用打印的 cDNA 微阵列来评估 16,000 个小鼠或人类基因。将使用激光捕获显微镜和微阵列评估肿瘤内特定细胞群的差异基因表达。将对 RAS 和 p53 基因进行突变测序，以发现肿瘤发生的分子引发剂。使用最先进的生物信息学对微阵列数据进行分析，以识别与市售参考 RNA 相比过度表达和表达不足的基因，从而允许进行类似研究的实验室之间进行标准化。基因数据将及时发布到我们的网站上以供数据共享。这些研究将提供人类牙源性肿瘤的首次详细突变和基因谱研究​​。