Comprehensive Analysis of Genetic Alterations in Oral Cancer

口腔癌基因改变的综合分析

• 批准号: 7855203
• 负责人: RICHARD A GIBBS
• 金额: $ 118.05万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7855203
• 关键词: Address; Affect; Behavior; Cancer Center; Cancer Etiology; Cataloging; Catalogs; Chromosomal Rearrangement; Chromosomal translocation; Chromosome Mapping; Clinical; Collaborations; Communities; Copy Number Polymorphism; Coupled; Custom; DNA; DNA Resequencing; DNA Sequence; Data; Data Set; Databases; Development; Diagnostic tests; Early Diagnosis; Event; Exons; Frequencies; Functional RNA; Gene Mutation; Genes; Genetic; Genetic Transcription; Genome; Genomic Instability; Genomics; Gingiva; Head and Neck Surgery; Hereditary Disease; Heterogeneity; Human; Human Genome; Individual; Knowledge; Libraries; Malignant - descriptor; Malignant Neoplasms; Medicine; Messenger RNA; MicroRNAs; Molecular; Molecular Profiling; Mouth Neoplasms; Mutation; Mutation Analysis; Normal tissue morphology; Operative Surgical Procedures; Oral; Oral cavity; Oral mucous membrane structure; Palate; Partner in relationship; Pathway interactions; Patients; Persons; Phase; Play; Radiation; Regulator Genes; Research; Research Proposals; Resolution; Resources; Role; Sample Size; Sampling; Site; Solid; Solid Neoplasm; Somatic Mutation; Squamous cell carcinoma; Sublingual Region; Survival Rate; Systems Biology; Techniques; Technology; Tissue Banking; Tissue Banks; Tongue; Tongue Squamous Cell Carcinoma; Translational Research; Tumor Tissue; Tumor-Derived; University of Texas M D Anderson Cancer Center; anticancer research; cancer genetics; cancer genome; chemotherapy; college; cost; design; epigenomics; gene function; genome sequencing; improved; insight; malignant mouth neoplasm; molecular marker; mouth squamous cell carcinoma; neoplastic cell; new therapeutic target; next generation; novel; outcome forecast; public health relevance; therapeutic target; tumor; tumor progression

DESCRIPTION (provided by applicant): Very little is known about the genetic alterations contributing o the development and progression of oral cancer. Currently, there are no large scale genomic studies addressing these issues, presumably owing to the cost and difficulties associated with such efforts. Yet knowledge of the underlying genetic causes of oral cancer is crucial to the design of targeted therapies and identification of molecular markers that may prove valuable in the prognosis or early detection. The overall objective of this research proposal is to generate a comprehensive database of the genomic alterations in oral cancer. Leveraging the strength of our extensive and well annotated tumor tissue bank at the University of Texas M.D. Anderson Cancer Center and cutting edge technology developed by Baylor College of Medicine's Human Genome Sequencing Center, we will perform somatic mutation analysis on over 6000 cancer-related genes and identify structural abnormalities over the whole genome for 100 cases of squamous cell carcinoma of the oral tongue (SCCOT). This study will generate information regarding genetic alterations present in SCOTT in unprecedented detail, including mutations, copy number alterations and chromosomal translocations. This single project has widespread potential to result in discovery of dozens of novel therapeutic targets for a cancer where the primary treatments are still surgery, chemotherapy and radiation. Moreover, identification of a panel of genes specifically altered in oral cancer is a critical step in developing diagnostic tests for personalized medicine to treat these devastating and often fatal cancers. At the conclusion of this study, SCCOT will be one of the most well characterized tumor types on the genomic level. PUBLIC HEALTH RELEVANCE: Oral cancer affects 300,000 persons worldwide each year, and the overall survival rate is just above 50%. All cancers are genetic diseases and a better understanding of the genetic alterations that cause cancer could be used to design more effective tumor-specific therapies. This study is a comprehensive large-scale examination of all the genetic changes found in tumors derived from patients with oral cancer and the information gained could have a major impact on the way we treat and detect these and other cancers.

描述（由申请人提供）：对于导致口腔癌发生和进展的基因改变知之甚少。目前，还没有大规模的基因组研究解决这些问题，大概是由于与此类努力相关的成本和困难。然而，了解口腔癌潜在的遗传原因对于设计靶向治疗和识别分子标记至关重要，这些分子标记可能对预后或早期检测有价值。该研究计划的总体目标是生成口腔癌基因组改变的综合数据库。借助德克萨斯大学 M.D. 安德森癌症中心广泛且注释完善的肿瘤组织库的优势以及贝勒医学院人类基因组测序中心开发的尖端技术，我们将对 6000 多个癌症相关基因进行体细胞突变分析，鉴定了 100 例口腔舌鳞状细胞癌 (SCCOT) 病例的全基因组结构异常。这项研究将以前所未有的详细程度生成有关 SCOTT 中存在的遗传改变的信息，包括突变、拷贝数改变和染色体易位。这个项目具有广泛的潜力，可以发现数十种针对主要治疗方法仍然是手术、化疗和放疗的癌症的新治疗靶点。此外，鉴定一组在口腔癌中特异性改变的基因是开发个性化医疗诊断测试的关键一步，以治疗这些毁灭性且往往致命的癌症。本研究结束时，SCCOT 将成为基因组水平上特征最明确的肿瘤类型之一。 公共卫生相关性：口腔癌每年影响全球 30 万人，总体生存率略高于 50%。所有癌症都是遗传性疾病，更好地了解导致癌症的基因改变可用于设计更有效的肿瘤特异性疗法。这项研究是对口腔癌患者肿瘤中发现的所有遗传变化的全面大规模检查，获得的信息可能对我们治疗和检测这些癌症和其他癌症的方式产生重大影响。