Molecular Determinants of Oral Cancer Detection

描述(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年生存率一直保持在大约30%-40%的低水平，并且一直是所有癌症死亡率中最差的之一。这是不恰当的，表明需要制定预防、诊断和治疗这一疾病的新战略。 这项建议旨在利用基因组和对患者群体的表达方法来利用口腔鳞癌的分子决定因素，这将允许最大限度地利用新兴技术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(LOH)和拷贝数异常(CNA)谱分析(AIM 1)和全面差异表达谱分析(AIM 2)的综合力量。这种协同方式的优势是显著的。例如，如果同一基因出现DNA拷贝数异常和表达变化，我们不仅可以独立验证图谱数据，还可以确定该基因表达变化的机制。此外，该特定基因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，以利用口腔鳞状细胞癌中一致和一致的分子决定因素(目标3)。 这项建议最佳地利用现有的患者资源和新兴技术来利用口腔鳞状细胞癌中一致和协调的基因组和转录决定因素。这将作为更广泛的以患者为基础的研究的试点项目和/或可行性测试，以识别和验证用于口腔/头颈部癌症早期检测的分子生物标志物。

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.