Phenotype and Gene Expression in Odontogenic Tumors

牙源性肿瘤的表型和基因表达

• 批准号: 7369707
• 负责人: John T. Wright
• 金额: $ 29.97万
• 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/7369707
• 关键词: Affect; Age of Onset; Ameloblastoma; Area; Arts; Automobile Driving; BRCA1 gene; Bioinformatics; Biological; Cells; Cessation of life; Characteristics; Childhood; Clinical; Common Neoplasm; Complex; Condition; Data; Dental; Development; Epithelium; Event; Excision; Foundations; Future; Gene Expression; Genes; Genotype; Growth; HRAS gene; Head and Neck Cancer; Head and Neck Neoplasms; Head and neck structure; High Prevalence; Histocompatibility Testing; Histology; Human; Human Genome; Imaging Techniques; Immunohistochemistry; In Situ Hybridization; Inherited; Internet; Invasive; Keratocyst; Knowledge; Laboratories; Lasers; Lead; Learning; Lesion; Localized; Location; Maintenance; Malignant - descriptor; Malignant neoplasm of pharynx; Mesenchyme; Microarray Analysis; Microdissection; Microscopy; Molecular; Molecular Genetics; Molecular Profiling; Morbidity - disease rate; Mouth Neoplasms; Mus; Mutate; Mutation; Neoplasms; Numbers; Odontogenic Tumors; Odontoma; Operative Surgical Procedures; Oropharyngeal; Pathway interactions; Phenotype; Play; Population; Printing; Process; Protein Overexpression; Proto-Oncogenes; RNA; Research; Research Personnel; Role; Site; Standardization; Stem cells; TP53 gene; Techniques; Testing; Thinking; Time; Tissue-Specific Gene Expression; Tissues; Tooth structure; Tumor Subtype; base; cDNA Arrays; cell type; malignant breast neoplasm; mouse model; mutant; neoplastic cell; novel; outcome forecast; programs; size; tumor; tumorigenesis; tumorigenic

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.

人类基因组的解开使我们对分子遗传学的认识迅速发展， 调节和决定正常和病理组织发育的控制。虽然进展 在简单的遗传条件的领域中，人们已经迅速而大量地了解到， 包括导致和驱动肿瘤发生的分子事件的条件。的发展 分子生物学技术可以同时分析大量基因， 可以有效且高效地评价不同组织和/或肿瘤之间的基因表达。 这些强大的分子技术允许新的实验进入之间的关系 正常和病理组织的表型和基因型。先前的研究表明， 和/或突变的RAS基因，以及肿瘤发生的位置， 细胞是局部的。我们推测，异质性牙源性肿瘤表型的结果， RAS和/或WNT途径下游的多个基因的差异表达。我们 我建议通过确定人类的牙源性肿瘤来验证这一假设， 多种病变包括成釉细胞瘤、牙源性角化囊肿和较少见的肿瘤 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 技术.肿瘤之间差异基因表达的表征将使用 cDNA微阵列打印评估16,000小鼠或人类基因。的差异性基因表达 将使用激光捕获显微镜和微阵列评估肿瘤内的特定细胞群。 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子。 使用最先进的生物信息学分析微阵列数据，以鉴定过度表达和表达不足的基因 与允许实验室之间标准化的市售参考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进行数据共享。 这些研究将提供第一个详细的突变和基因概况研究人类牙源性 肿瘤的