Effect of cooperating mutations and genetic background on colon cancer metastasis

协同突变和遗传背景对结肠癌转移的影响

基本信息

批准号：
8705902
负责人：
Rachel Marie Lynch
金额：
$ 5.7万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8705902
关键词：
Adenocarcinoma Adenomatous Polyps Adenoviruses Affect Alleles Benign Body part CTNNB1 gene Cancer Etiology Cancer Patient Carcinoma Cessation of life Clinical Colon Colon Carcinoma Colonic Adenoma Colonic Neoplasms Colorectal Cancer Colorectal Neoplasms Developed Countries Development Disease Distal Distant Dominant Genetic Conditions Epithelium Event Gene Expression Profiling Gene Mutation Genetic Genetic Polymorphism Genotype Goals Human Hybrids Inbred Strain Individual Intervention Invaded Investigation KRAS2 gene Liver Liver diseases Longevity Malignant Neoplasms Metastatic Carcinoma Metastatic to Modeling Molecular Profiling Monitor Morphology Mouse Strains Mus Mutation Neoplasm Metastasis Patients Predisposition Primary Neoplasm Research Risk Role Secondary to Site TP53 gene Testing Therapeutic Time Tissues United States Variant WNT Signaling Pathway base cancer cell effective intervention high risk improved malignant breast neoplasm mortality mouse model recombinase trait transcriptomics tumor tumor growth tumor initiation tumor progression

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States, with mortality almost exclusively attributed to metastatic liver disease. Therefore, understanding the mechanisms governing how a primary tumor grows and disseminates to secondary sites is of great clinical importance. There is increasing evidence suggesting that genetic background is an important determinant of metastatic susceptibility, but little is known about the specific genetic factors that affect CRC. The proposed research will develop a mouse model of CRC that will allow the investigation of whether genetic background influences tumor development, progression, and metastases through interaction with specific transforming mutations. Tumor growth, histopathological analysis, and gene expression analysis will be used to characterize cancer development in the new model and compare it to an existing CRC mouse model that utilizes a different tumor initiating event. Similar analyses will be performed on mice with differing maternal genotypes and cooperating mutations to investigate how the mutations and genetic background interact to influence tumor progression. The long-term goal of this research is to be able to predict which patients have a higher risk of metastatic disease and develop more appropriate therapeutic strategies for these individuals.

描述（由申请人提供）：结直肠癌（CRC）是美国与癌症相关死亡的第二大原因，死亡率几乎完全归因于转移性肝病。因此，理解管理原发性肿瘤如何生长和传播到次要部位的机制至关重要。越来越多的证据表明，遗传背景是转移性敏感性的重要决定因素，但对影响CRC的特定遗传因素知之甚少。拟议的研究将开发CRC的小鼠模型，该模型将通过与特定转化突变的相互作用来研究遗传背景是否会影响肿瘤的发展，进展和转移。肿瘤生长，组织病理学分析和基因表达分析将用于表征新模型中的癌症发展，并将其与使用不同肿瘤起始事件的现有CRC小鼠模型进行比较。将对具有不同母体基因型和合作突变的小鼠进行类似的分析，以研究突变和遗传背景如何相互作用以影响肿瘤进展。这项研究的长期目标是能够预测哪些患者患转移性疾病的风险更高，并为这些人制定更合适的治疗策略。