Molecular Determinants of Oral Cancer Detection

描述（由申请人提供）：口腔鳞状细胞癌（SCC）是全球第六大常见癌症，占男性癌症的4%和女性癌症的2%。在美国，每年有超过38，000例新的口腔癌病例。在过去的几十年里，口腔癌的总体5年生存率一直很低，约为30-40%，并且仍然是所有癌症死亡率中最差的。这是令人失望的，并指出需要新的战略，预防，诊断和治疗这种疾病。 该提案旨在利用患者人群的基因组和表达方法来利用口腔SCC的分子决定因素，这将允许新兴技术的最大效用来识别口腔癌中一致的基因组和转录决定因素。将利用基于SNP阵列的杂合性丢失（洛）和拷贝数异常（CNA）分析（Aim 1）以及综合差异表达分析（Aim 2）的组合功效。这类协同办法的优点是显著的。例如，如果同一个基因显示DNA拷贝数异常和表达改变，我们不仅可以独立验证分析数据，还可以确定该基因表达改变的机制。此外，该特定基因将更有可能具有生物学意义。生物信息学工具和生物计算专业知识已经到位，可以利用口腔SCC中一致和一致的分子决定因素（目标3）。 该提案最佳地利用现有的患者资源和新兴技术，利用口腔SCC中一致和一致的基因组和转录决定簇。这将作为一个试点项目和/或可行性测试，用于更广泛的以患者为基础的研究，以确定和验证用于早期检测口腔/头颈癌的分子生物标志物。

DESCRIPTION (provided by applicant): Oral squamous cell carcinoma (SCC) is the sixth most common cancer worldwide accounting for 4% of cancers in men and 2% of cancers in women. In the United States there are over 38,000 new cases of oral cancer each year. The overall 5-year survival rates for oral cancer have remained low at approximately 30-40% for the past decades and has remain among the worst of all cancer death rates. This is dispointing and points to the needs for new strategy for prevention, diagnosis and treatment of this disease. This proposal aims to harness the molecular determinants of oral SCC using genomic and expressional approaches on patient population that will permit the maximal utility of emerging technologies to identify concordant genomic and transcriptional determinants in oral cancer. The combined power of SNP array-based loss of heterozygosity (LOH) and copy number abnormalities (CNA) profiling (Aim 1) and the comprehensive differential expression profiling (Aim 2) will be utilized. The advantages of this type of synergistic approach are significant. For example, if the same gene shows DNA copy number abnormalities and altered expression, not only do we have independent validation of the profiling data but we will also have determined the mechanism of altered expression of that gene. Furthermore, that particular gene will be more likely to have biological significance. Bioinformatics tools and biocomputational expertise are in place to harness the consistent and concordant molecular determinants in the oral SCC (Aim 3). This proposal optimally utilizes existing patient resources and emerging technologies to harness consistent and concordant genomic and transcriptional determinants in oral SCC. This will serve as a pilot project and/or feasibility test for more extensive patient-based studies to identify and validate molecular biomarkers for early detection of oral/head and neck cancer.