Mitochondrial Genome Analysis to Detect Aggressive Behavior of Premalignant Color

线粒体基因组分析检测癌前颜色的攻击行为

基本信息

批准号：
8536869
负责人：
Felix O Aikhionbare
金额：
$ 10.24万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
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：
2012-09-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8536869
关键词：
Address Adenomatous Polyposis Coli Adenomatous Polyps African American Aggressive behavior Architecture Biological Models Blood specimen Cancer Patient Caucasians Caucasoid Race Cell Adhesion Cells Cessation of life Classification Clinical Colon Colon Adenocarcinoma Colon Carcinoma Colonic Adenoma Color Colorectal Colorectal Adenocarcinoma Colorectal Adenoma Colorectal Cancer Colorectal Neoplasms Complex DNA Development Diagnosis Diagnostic Neoplasm Staging Disease Disease Outcome Epithelial Epithelial Cells Gene Mutation General Population Genes Genetic Genetic Polymorphism Goals Heterogeneity Histocompatibility Testing Histologic Human Incidence Individual Journals Knowledge Lead Link Malignant Neoplasms Malignant neoplasm of ovary Methods Minority Mismatch Repair Mitochondria Mitochondrial DNA Mitochondrial Proteins Modality Molecular Molecular Profiling Mutation Mutation Detection Neoplasm Metastasis Neoplastic Cell Transformation Outcome Oxidative Phosphorylation Pathology Patients Pattern Play Population Predictive Factor Predisposition Premalignant Process Protein Subunits Proteins Qualifying Reactive Oxygen Species Rectal Adenoma Reporting Research Role Signal Transduction Staging Stratification Subgroup Surveys Survival Rate Technology Testing Tissues Transcriptional Activation Tubular formation Tubulovillous Adenoma Tumor Suppressor Proteins Tumor Tissue Tumor stage United States Variant Villous Villous Adenoma Woman Work cancer cell cancer therapy caucasian American clinically relevant clinically significant deep sequencing gastrointestinal genome analysis high risk high throughput analysis improved innovation liquid chromatography mass spectrometry men mitochondrial DNA mutation mitochondrial genome mortality outcome forecast oxidative DNA damage phrases polyposis protein expression racial difference racial/ethnic difference research study tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the United States and it is commonly diagnosed in both men and women. It was estimated that 146,940 new cases were diagnosed, and 56,730 deaths from CRC occurred in 2010. The optimal management of patients with colorectal adenomatous polyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. While a number of treatment modalities have been developed for CRC, we still are far from finding why there are a great deal of heterogeneity show by CRC patients during the course and outcome regarding the disease racial differences. Therefore, more research is needed not only to understand the basic processes that are subverted by early stages of CRC cells to gain a proliferative advantage, also why there are a great deal of racial differences show by CRC patients during the course and outcome of the disease. The accumulation of ROS and oxidative DNA damage during the course of a lifetime may be deleterious and lead to specific mitochondrial genome alterations that may be associated in the progression of CRC. Our central hypothesis is that mtDNA gene profiling in primary tissues of colorectal adenomatous polyps will identify clinically relevant patterns of mutations and expression in histological colorectal tumor stages and subgroups of Caucasian and African-American with aggressive tumors. Specific aims are: (i) to determine and evaluate the role of mtDNA polymorphism/mutations play between African American and Caucasian patients susceptibility to the progression of CRC. (ii); to determine whether there are differences in the level of mitochondrial protein expression profiles between "early" stages of colorectal tumors and normal surrounding colorectal tissue from individual patients of African-American and Caucasian origin. This study is different from other previous studies in that a multiplatform of technologies will be performed to accurately evaluate genetic changes in epithelial colorectal adenopolyps and sub-classification of patients with similar disease, correlating the results with racial/ethnical populations. Results from this study should provide basic knowledge to the development of proper clinical tests for prediction of CRC progression in patients' clinical outcome, which is required for efficacious therapies.

描述（由申请人提供）：结直肠癌（CRC）是美国最常见的胃肠道恶性肿瘤，通常在男性和女性中被诊断出来。据估计，诊断出146,940例新病例，2010年发生了56,730例CRC死亡。结直肠腺瘤息肉患者的最佳管理取决于适当分期策略的准确性，因为具有相似的结直肠腺癌结构的患者在疾病和结果中显示出异质性。尽管CRC已经开发了许多治疗方式，但我们仍然远没有发现为什么CRC患者在课程期间出现了很多异质性，以及有关疾病种族差异的结果。因此，需要更多的研究不仅需要了解CRC细胞的早期阶段来颠覆的基本过程以获得增殖的优势，这也是为什么种族差异很大的原因表明在病程和疾病结果期间由CRC患者组成。 ROS的积累和氧化性DNA损伤在一生过程中可能是有害的，并导致特定的线粒体基因组改变，这可能与CRC的进展有关。我们的中心假设是，结直肠腺瘤息肉原代组织中的mtDNA基因分析将确定具有积极肿瘤的高加索人和非裔美国人的组织学结肠直肠肿瘤阶段的突变和表达的临床相关模式和表达。具体目的是：（i）确定和评估MTDNA多态性/突变在非裔美国人和高加索患者对CRC进展的敏感性之间起作用。（ii）;确定结直肠肿瘤的“早期”阶段之间的线粒体蛋白表达谱与非裔美国人和白种人起源的单个患者的正常结直肠组织之间存在差异。这项研究与以前的其他研究不同，因为将进行倍增技术以准确评估上皮结直肠腺瘤的遗传变化以及类似疾病的患者的亚分类，从而将结果与种族/种族群体相关联。这项研究的结果应为开发适当的临床测试提供基本知识，以预测患者临床结果的CRC进展，这是有效疗法所必需的。