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

• 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
• 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

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(申请人提供)：结直肠癌(CRC)是美国最常见的胃肠道恶性肿瘤，男性和女性均可确诊。据估计，2010年诊断出146,940个新病例，56,730人死于儿童权利委员会。结直肠腺瘤性息肉患者的最佳治疗依赖于适当的分期策略的准确性，因为具有相似结直肠腺癌结构的患者在疾病的过程和结果上表现出异质性。虽然已经开发了许多治疗结直肠癌的方法，但我们仍然远未发现为什么结直肠癌患者在疾病过程和转归方面表现出很大的种族差异。因此，不仅需要更多的研究来了解CRC细胞早期阶段颠覆获得增殖优势的基本过程，而且还需要更多的研究来了解为什么会有大量的种族差异显示出来 由结直肠癌患者在病程和转归过程中决定。一生中ROS的积累和DNA的氧化损伤可能是有害的，并导致特定的线粒体基因组改变，这可能与结直肠癌的进展有关。我们的中心假设是，大肠腺瘤性息肉原发组织中的mtDNA基因图谱将确定大肠肿瘤组织学分期和具有侵袭性肿瘤的高加索人和非裔美国人亚群中与临床相关的突变和表达模式。具体目标是：(I)确定和评估线粒体DNA多态/突变在非裔美国人和高加索人患者对结直肠癌进展的易感性中所起的作用。(Ii)；确定非裔美国人和高加索血统的个别患者的“早期”大肠肿瘤组织和周围正常大肠组织的线粒体蛋白表达谱水平是否存在差异。这项研究与以前的其他研究的不同之处在于，将实施多平台技术来准确评估上皮性结肠腺息肉的基因变化，并对患有类似疾病的患者进行细分，将结果与种族/民族人口相关联。这项研究的结果应该为开发适当的临床测试以预测患者临床结果的CRC进展提供基础知识，这是有效治疗所必需的。