Genome-wide Exploration of DNA Methylation Markers for Thyroid Cancer

甲状腺癌 DNA 甲基化标记的全基因组探索

基本信息

批准号：
8492305
负责人：
MICHAEL Mingzhao XING
金额：
$ 21.14万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8492305
关键词：
Aberrant DNA Methylation Adult Area Autoantibodies Benign Biological Assay Biopsy Specimen Blood Tests Blood specimen Cancer Patient Characteristics Clinical DNA DNA Methylation Development Diagnosis Diagnostic Diagnostic Procedure Diagnostic Sensitivity Diagnostic Specificity Effectiveness Endocrine Evaluation Fine needle aspiration biopsy General Population Genes Genome Goals Human Hypothyroidism Incidence Laboratories Lead Life Malignant - descriptor Malignant Neoplasms Malignant neoplasm of thyroid Medicine Methylation Molecular Monitor Needle biopsy procedure Nodule Operative Surgical Procedures Papillary thyroid carcinoma Patients Pattern Postoperative Period Prevalence Primary Neoplasm Principal Investigator Protocols documentation Publishing Research Rest Sampling Sensitivity and Specificity Serum Specimen System Technical Expertise Techniques Test Result Testing Thyroglobulin Thyroglobulin antibody Thyroid Gland Thyroid Nodule Thyroidectomy Time Tumor Tissue Ultrasonography base cancer recurrence experience genome wide methylation genome-wide molecular marker novel novel diagnostics novel strategies prognostic promoter public health relevance success thyroid neoplasm tumor

项目摘要

DESCRIPTION (provided by applicant): Thyroid cancer is the most common endocrine malignancy with a rapid rising incidence in recent years, which is largely attributable to the increased diagnosis of thyroid nodules. There are several areas in thyroid tumor medicine in which efficiency and effectiveness of patient management are limited with the current standard approaches. For example, the widely used fine needle aspiration biopsy (FNAB) for thyroid nodule evaluation often yields indeterminate cytological findings, leading to unnecessary thyroid surgery; the standard serum thyroglobulin (Tg) testing to monitor thyroid cancer recurrence is often hampered by the presence of autoantibodies against Tg in the serum; and the current prognostic evaluation of thyroid cancer using clinicopathological criteria is often uncertain, particularly preoperatively. Novel thyroid diagnostic and prognostic molecular markers, if available, could help circumvent these clinical obstacles. As aberrant DNA methylation patterns are often specifically associated with human cancers, we hypothesize that unique DNA methylation patterns or alterations also exist in thyroid cancer and could be used as reliable molecular markers for this cancer. To test this hypothesis, in the present project we propose to use a recently developed powerful 450K DNA methylation microarray system to perform genome-wide search for aberrant DNA methylation alterations in thyroid tumors to identify panels of most prominent DNA methylation markers that have the highest diagnostic and prognostic potential with the best specificities and sensitivities for thyroid cancer. We will then test them on FNAB and serum specimens collected from thyroid tumor patients with the goal to establish novel clinical diagnostic and prognostic molecular tests for the management of thyroid nodules and thyroid cancer. This project represents a novel approach using a powerful experimental system to identifying DNA methylation molecular markers for thyroid cancer, which is expected to have a significant impact on the current practice of thyroid tumor medicine. The research team and their laboratory are well experienced and equipped with both technical expertise and thyroid tumor patient specimens required to successfully pursue the proposed studies.

描述（由申请人提供）：甲状腺癌是最常见的内分泌恶性肿瘤，近年来发病率迅速上升，这在很大程度上归因于甲状腺结节的诊断增加。甲状腺肿瘤医学有几个领域，其中患者管理的效率和有效性受到当前标准方法的限制。例如，用于甲状腺结节评估的广泛使用的细针吸入活检（FNAB）通常会产生不确定的细胞学发现，从而导致不必要的甲状腺手术。标准的血清甲状腺球蛋白（TG）测试以监测甲状腺癌复发，通常会因在血清中对TG的自身抗体存在而阻碍。当前使用临床病理学标准对甲状腺癌的预后评估通常不确定，尤其是术前。新型甲状腺诊断和预后分子标记物（如果有）可以帮助避免这些临床障碍。由于异常的DNA甲基化模式通常与人类癌症特别相关，因此我们假设甲状腺癌中也存在独特的DNA甲基化模式或改变，并且可以用作该癌症的可靠分子标记。为了检验这一假设，在本项目中，我们建议使用最近开发的功能强大的450K DNA甲基化微阵列系统，以对甲状腺肿瘤中异常DNA甲基化改变进行全基因组的搜索，以识别具有最高诊断诊断最高的DNA甲基化标记的面板以及对甲状腺癌的最佳特异性和敏感性的预后潜力。然后我们会测试它们对从甲状腺肿瘤患者收集的FNAB和血清标本，其目标是建立新的临床诊断和预后分子测试，以治疗甲状腺结节和甲状腺癌。该项目代表了一种使用强大的实验系统来鉴定甲状腺癌的DNA甲基化分子标记物的新型方法，甲状腺癌有望对当前甲状腺肿瘤医学的实践产生重大影响。研究小组及其实验室经验丰富，并配备了技术专业知识和甲状腺肿瘤患者标本，才能成功进行拟议的研究。