TWO HIT GENE MAPPING IN RENAL CELL CARCINOMA

肾细胞癌中的两个命中基因图谱

基本信息

批准号：
8638363
负责人：
James Dowling MCKAY
金额：
$ 12.62万
依托单位：
INTERNATIONAL AGENCY FOR RES ON CANCER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8638363
关键词：
Alleles Biological Biological Assay Blood Cancer-Predisposing Gene Candidate Disease Gene Case-Control Studies Chromosome Mapping Code Constitutional DNA Data Dependency Development Disease susceptibility Environmental Exposure Etiology Event Family Frequencies Gene Mutation Genes Genetic Predisposition to Disease Genetic Risk Genetic Variation Genome Genomics Germ Lines Individual Inherited International International Agency for Research on Cancer Investigation Knowledge Malignant Neoplasms Maps Massive Parallel Sequencing Modeling Mutation Pathway interactions Patients Persons Phase Population Predisposition Renal Cell Carcinoma Renal carcinoma Research Design Resected Risk Risk Management Sample Size Scanning Series Somatic Mutation Statistical Methods Susceptibility Gene Techniques Testing The Cancer Genome Atlas Tissues Tumor Tissue Variant base cancer genome cancer risk cancer type carcinogenesis cost design exome exome sequencing genetic variant genome wide association study genome-wide genome-wide analysis mutant novel public health relevance rare variant repository tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): The germ-line genetic variants identified thus far generally explain only part of the predicted genetic risk for most cancers, including renal cell carcinoma (RCC). A component of the remaining risk may be explained by functionally consequent genetic variants that are individually very rare (or private). The contribution that thi spectrum of genetic variation makes to susceptibility to RCC remains unexplored. Strategies that allow for agnostic, genome-wide assessment of such variants are likely to require very important sample sizes for adequate statistical power. In addition to the large cost, such study approaches may not be practical for rare cancers due to the lack of sufficiently large bio-repositories. Unusual frequencies of "two-hit" mutation events (one mutation in the germ-line, and a second, somatic mutation in the same individual) may be able to map genes involved in RCC cancer susceptibility. Within the exceptional IARC RCC bio-repository, we propose to use this "two-hit mapping" approach in a discovery and replication study design to identify genes involved in genetic susceptibility to RCC acting via Knudson's two hit model.

描述（由申请人提供）：迄今为止确定的种系遗传变异通常仅解释大多数癌症的遗传风险的一部分，包括肾细胞癌（RCC）。剩余风险的一个组成部分可以通过功能上非常罕见（或私人）的遗传变异来解释。遗传变异频谱对RCC敏感性的贡献仍未得到探索。允许对此类变体进行不可知论，全基因组评估的策略可能需要非常重要的样本量才能获得足够的统计能力。除了巨大的成本外，由于缺乏足够大的生物重新定位，这种研究方法对于罕见的癌症可能不实。 “两击”突变事件的异常频率（种系中的一个突变和同一个体中的第二个体细胞突变）可能能够映射参与RCC癌敏感性的基因。在杰出的IARC RCC生物依赖者中，我们建议在发现和复制研究设计中使用这种“两次映射”方法，以识别涉及通过Knudson的两个命中模型对RCC作用的遗传敏感性涉及的基因。