The role of promoter hypermethylation in adenoid cystic carcinoma

启动子高甲基化在腺样囊性癌中的作用

• 批准号: 7301693
• 负责人: Patrick Kyongmin Ha
• 金额: $ 13.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7301693
• 关键词: Adenoid Cystic Carcinoma; Adjuvant Radiotherapy; Adjuvant Therapy; Affect; Basic Science; Behavior; Biological Assay; Biological Markers; Candidate Disease Gene; Cell Line; Clinical; Data; Development; Disease; Distant; Distant Metastasis; Epigenetic Process; Event; Excision; Fingerprint; Foundations; Future; Gene Silencing; Gene Targeting; Genes; Genetic; Genome; Goals; Hypermethylation; Indolent; K-Series Research Career Programs; Knowledge; Lead; Malignant Epithelial Cell; Malignant Neoplasms; Mentorship; Methylation; Minor salivary gland structure; Molecular; Mutation; Operative Surgical Procedures; Otolaryngology; Outcome; Pathogenesis; Pathway interactions; Patients; Play; Primary Neoplasm; Process; Public Health; Publishing; Radiation therapy; Recording of previous events; Recurrence; Research; Research Personnel; Resistance; Role; Salivary; Salivary Glands; Sampling; Screening procedure; Serum; Solid Neoplasm; Standards of Weights and Measures; Suppressor Genes; Techniques; Testing; Therapeutic Intervention; Tissue Sample; Training; Tumor Suppressor Genes; Tumor-Suppressor Gene Inactivation; Work; carcinogenesis; chemotherapeutic agent; chemotherapy; clinically relevant; cohort; improved; insight; novel; novel therapeutics; prognostic; programs; promoter; research study; skills training; therapeutic target; tumor; tumorigenesis

DESCRIPTION (provided by applicant): The candidate, Dr. Ha, has demonstrated a long standing history of commitment to research and academic otolaryngology. This career development award, under the mentorship of Drs. David Sidransky and Joseph Califano is focused on the basic mechanisms underlying adenoid cystic carcinoma (ACC). ACC is a salivary gland malignancy characterized by persistent local, regional, and distant recurrence despite complete surgical resection and adjuvant radiotherapy. Attempts at improving loco regional control with chemotherapy have been disappointing, and to date, no systemic agent improves control of regional or distant metastases. Better characterization of the genetic alterations involved in ACC tumorigenesis will give us insight into the selection of effective adjuvant therapies or the development of novel therapy. Promoter hypermethylation as a means of tumor suppressor gene silencing is a significant factor in solid tumor carcinogenesis. We have preliminary evidence that promoter hypermethylation is an important means of tumor suppressor gene inactivation in ACC. The candidate proposes to evaluate commonly methylated tumor suppressor genes in an expanded cohort of ACC samples as well as perform genome wide screening in ACC cell lines in an effort to identify novel methylated genes. Functional and clinical correlation will then be applied to evaluate the biologic significance and prognostic value of these inactivated genes. The goal of this work is to comprehensively analyze the role of promoter hypermethylation in ACC. The impact on public health lies in establishing this groundwork that will lead to the identification of important biomarkers of tumor behavior and possible avenues of therapeutic intervention in the treatment of this disease. The process of performing these experiments will provide the candidate with the necessary guidance, coursework, and practical training towards becoming an independent investigator as well as furthering the basic science knowledge of adenoid cystic carcinoma.

描述（由申请人提供）：候选人Dr. Ha在耳鼻喉科的研究和学术方面有着悠久的历史。这个职业发展奖项，在dr。David Sidransky和Joseph Califano专注于腺样囊性癌（ACC）的基本机制。