Genetic and molecular characterization of kidney cancer

肾癌的遗传和分子特征

• 批准号: 6799218
• 负责人: ALLAN J PANTUCK
• 金额: $ 12.72万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-23 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6799218
• 关键词: biomarker; chromosome aberrations; clinical research; comparative genomic hybridization; fluorescent in situ hybridization; gene expression; gene mutation; genetic markers; human genetic material tag; human tissue; immunocytochemistry; laser capture microdissection; metastasis; microarray technology; molecular biology information system; molecular oncology; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplasm /cancer immunotherapy; neoplastic process; polymerase chain reaction; renal cell carcinoma; tumor suppressor genes

DESCRIPTION (provided by applicant): Financial support and protected time is requested to support a career development program comprised of mentored clinical research and formal course work leading to a Masters in Clinical Research from a Graduate Training Program in Translational Investigation (K30). The long-term career objective of this grant application is to become a successful, independent clinical investigator in urological oncology focussing on patient-oriented research, ultimately leading to a tenured faculty position. The proposed research project will serve as a tool from which to gain mentored research experience. The overall goal of the proposed research is to combine the extensive clinical and experimental resources in kidney cancer at UCLA School of Medicine to identify the genetic and molecular signature of response to immunotherapy for patients with metastatic renal cell carcinoma (RCC). Although some aspects of the molecular genetics of RCC have begun to be appreciated, little is known about the genes and proteins underlying its unpredictable clinical course and whether or not an individual patient will or will not respond to immunotherapy. The resources at UCLA provide a unique opportunity to take advantage of new genome wide discovery tools (e.g., expression arrays, genomic databases) which will provide new strategies to tackle tumor classification and tumor biology. The combination of a strong clinical database, mRNA expression array studies from fresh tumor samples, comparative genomics and gene sequencing, and large archived tissue sample resources organized in a tissue array format may provide new tools to uncover novel aspects of RCC biology. I propose to use chromosomal analysis (aim 1), VHL mutation analysis (aim 2), as well as molecular profiling of global gene expression patterns (aim 3) to identify genetic and molecular markers for kidney cancer progression, metastasis, and response to immunotherapy. Lastly, human tissue arrays and an extensive clinical database will be used to externally validate the experimental markers (aim 4). Ultimately, this proposal is a platform from which I seek training to further a career in cancer research at the clinical/translational interface of oncologic care with a special interest in gene and immune-based therapies for renal cell carcinoma.

描述（由申请人提供）：财务支持和保护时间 要求支持职业发展计划，其中包括受指导的 临床研究和正式课程学习，获得临床硕士学位 转化研究研究生培训项目的研究 （K30）。此补助金申请的长期职业目标是成为 泌尿肿瘤学领域成功的独立临床研究者 专注于以患者为导向的研究，最终导致终身教授 教职职务。拟议的研究项目将作为一个工具 从而获得指导性的研究经验。拟议的总体目标 研究是结合广泛的临床和实验资源 加州大学洛杉矶分校医学院的肾癌鉴定遗传和分子 转移性肾细胞患者对免疫治疗的反应特征 癌（RCC）。尽管 RCC 分子遗传学的某些方面已 开始受到重视，但对基因和蛋白质知之甚少 其不可预测的临床过程以及个人是否 患者会对免疫疗法产生反应或不会产生反应。加州大学洛杉矶分校的资源 提供利用新的全基因组发现的独特机会 工具（例如表达阵列、基因组数据库）将提供新的 解决肿瘤分类和肿瘤生物学的策略。组合 强大的临床数据库，来自新鲜肿瘤的 mRNA 表达阵列研究 样本、比较基因组学和基因测序以及大型存档组织 以组织阵列格式组织的样本资源可以提供新的工具 揭示 RCC 生物学的新颖方面。我建议使用染色体分析 （目标 1）、VHL 突变分析（目标 2）以及分子谱分析 全局基因表达模式（目标 3），以识别遗传和分子 肾癌进展、转移和反应的标志物 免疫疗法。最后，人体组织阵列和广泛的临床数据库 将用于外部验证实验标记（目标 4）。 最终，这个提案是我寻求培训以进一步发展的平台。 在临床/翻译界面从事癌症研究的职业 肿瘤护理，对基因和免疫疗法特别感兴趣 肾细胞癌。