Molecular and Epidemiologic Characterization of Salivary Gland Carcinomas

描述(申请人提供)：涎腺恶性肿瘤仅占美国所有头颈部恶性肿瘤的1-2%。他们的行为可能会非常不同，治疗通常需要手术和放射治疗。由于对这些罕见肿瘤的分子机制知之甚少，化疗和其他靶向治疗尚未被证明是有效的。作为这项合作计划的一部分，我们的目标是评估启动子甲基化作为一种使用新的微阵列技术抑制肿瘤抑制基因沉默的方法的作用。我们打算使用Illumina人类甲基化27阵列，该阵列能够采样超过14,000个基因的甲基化状态。然后，我们可以验证识别的靶点，并继续对它们在这些恶性肿瘤中的生物学相关性进行进一步的机械性研究。进行这一综合分析将使我们能够确定表观遗传沉默在唾液腺癌发生中的作用。公共卫生相关性：这笔赠款的目标是帮助确定甲基化在唾液腺癌症中的重要性，希望提供可用于预后或筛查的治疗目标或疾病标记物。

DESCRIPTION (provided by applicant): Salivary gland malignancies represent only 1-2% of all head and neck malignancies in the United States. Their behavior can be quite variable, and treatment usually involves surgery and radiation therapy. Because not much is known about the molecular mechanisms of these unusual tumors, chemotherapy and other targeted therapies have not been shown to be effective. As part of this collaborative proposal, our aim is to evaluate the role of promoter methylation as a means of tumor suppressor gene silencing using new microarray technology. We intend to use the Illumina Human Methylation27 array which is able to sample the methylation status of over 14,000 genes. We can then validate the identified targets and go on to perform further mechanistic studies of their biologic relevance in these malignancies. Performing this comprehensive analysis will allow us to determine the effect of epigenetic silencing on the carcinogenesis of salivary gland cancers. PUBLIC HEALTH RELEVANCE: The goal of this grant is to help identify the significance of methyaltion in salivary gland cancers with the hopes of providing either therapeutic targets or markers for disease that can be used for prognosis or screening.