Phenotype and Gene Expression in Odontogenic Tumors

人类基因组的解开导致了我们对分子遗传学知识的快速进步 调节和决定正常和病理组织发育的控制。在取得进展的同时 在简单遗传条件方面迅速和实质性的研究，对复杂遗传条件的了解要少得多 条件，包括导致和推动肿瘤发生的分子事件。的发展。 允许同时分析大量基因的分子生物学技术现在使它 有可能有效和高效地评估不同组织和/或肿瘤之间的基因表达。 这些强大的分子技术使人们可以通过新的实验来研究 正常组织和病理组织的表型和基因型。先前的研究表明过度表达 牙源性肿瘤中RAS基因突变与肿瘤发生的关系 细胞被本地化。我们假设不同的牙源性肿瘤表型是由 RAS和/或WNT通路下游的多个基因的差异表达。我们 建议通过确定具有表型的人类的牙源性肿瘤来检验这一假说 不同的病变包括成釉细胞瘤、牙瘤、牙源性角化囊肿和较少见的肿瘤 类型。将通过临床、组织学和成像来确定所有肿瘤的详细表型特征。 技巧。肿瘤之间差异基因表达的特征将通过使用 印制的用于评估16,000个小鼠或人类基因的基因芯片。基因表达的差异 肿瘤内的特定细胞群将使用激光捕获显微镜和微阵列进行评估。 将对RAS和P53基因进行突变测序，以发现肿瘤发生的分子启动者。 使用最先进的生物信息学分析微阵列数据以识别表达过高和表达不足的基因 与允许实验室之间标准化的商业可获得的参考RNA相比 进行类似的研究。基因数据将及时放在我们的网站上，以便于数据共享。 这些研究将首次提供人类成牙的详细突变和基因图谱研究。 肿瘤。

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.