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Genetic Basis of Familial Colorectal Cancer Type X

家族性结直肠癌 X 型的遗传基础

基本信息

批准号：
8719739
负责人：
Leon Raskin
金额：
$ 22.44万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-20 至 2016-04-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8719739
关键词：
Americas Applications Grants Australia Bioinformatics Cancer Biology Cancer Patient Cancer-Predisposing Gene Candidate Disease Gene Cells Code Colon Colorectal Cancer Complementary DNA Computer software Custom DNA Resequencing Data Development Disease Etiology Family Family member Founder Generation Frequencies Future Gene Mutation General Population Genes Genetic Genome Genomic DNA Genotype Goals Hereditary Malignant Neoplasm Hereditary Nonpolyposis Colorectal Neoplasms Heritability Human Genome Individual Inherited Intestines Lead Malignant Neoplasms Massive Parallel Sequencing Mentors Micellar Electrokinetic Capillary Chromatography Mutation Mutation Analysis Mutation Spectra Pathway interactions Patients Penetrance Phase Phenotype Prevention Proteins Quality Control RNA Interference Reading Risk Sampling Sequence Analysis Series Source Syndrome Variant abstracting age related base cancer therapy cancer type case control cohort colon cancer family registry cost exome exome sequencing high throughput technology mutant novel population based rare variant segregation

项目摘要

Abstract The overall goal of the proposed study is to identify new genes harboring rare mutations that considerably increase the risk of colorectal cancer (CRC). These mutations can underlie the observed familial aggregation of Lynch syndrome-like colorectal cancer cases called Familial Colorectal Cancer Type X (FCCTX). FCCTX is a Mendelian cancer syndrome with dominant mode of inheritance and incomplete penetrance. The first aim of the mentored-phase of this application is to identify novel candidate genes associated with risk of colorectal cancer in FCCTX patients using selective capture of protein-coding sequences in the human genome ("exome") followed by massively parallel resequencing of 10 patients with FCCTX. This approach has recently been successful in identifying novel genes causing Mendelian diseases. The identified candidate variants will be genotyped in the family members of the individuals with sequenced exomes for segregation analysis. During independent (R00) phase, the candidate genes will be resequenced in a large number of colorectal cancer cases and controls to find the spectrum of mutations in sporadic colorectal cancer and their presence in general population. In addition, the candidate genes will be resequenced in a large cohort of FCCTX families to find other individuals carrying mutations in these genes. The new genes and potentially pathways involved into development of colorectal cancer can become potential targets for colorectal cancer therapy. The proposed study represents also a proof of concept for the new strategy of exome resequencing for detecting of cancer predisposing genes. The low-cost, high throughput technologies for exome resequencing may facilitate the discovery of new candidate genes and mutations in familial cancer.

摘要