Mitochondrial Genome Analysis to Detect Aggressive Behavior of Premalignant Color

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，常见于男性和女性。据估计，2010年诊断出146，940例新病例，56，730例死于CRC。结直肠腺瘤性息肉患者的最佳治疗取决于适当分期策略的准确性，因为具有相似结直肠腺癌结构的患者在病程和预后方面表现出异质性。虽然已经为CRC开发了许多治疗模式，但我们仍然远远没有找到为什么CRC患者在病程和结局方面表现出大量的异质性。因此，需要更多的研究，不仅要了解被早期阶段的CRC细胞颠覆以获得增殖优势的基本过程，还要了解为什么存在大量的种族差异， CRC患者在疾病过程和结局期间的行为。在一生中ROS的积累和氧化性DNA损伤可能是有害的，并导致可能与CRC进展相关的特定线粒体基因组改变。我们的中心假设是，在大肠腺瘤性息肉的原发组织中的mtDNA基因谱将确定临床相关的突变模式和表达的组织学大肠肿瘤阶段和亚组的白人和非洲裔美国人与侵袭性肿瘤。具体目标是：（i）确定和评估mtDNA多态性/突变在非裔美国人和高加索人患者对CRC进展的易感性之间的作用。(ii)以确定是否有差异的线粒体蛋白质表达谱的水平之间的“早期”阶段的结直肠肿瘤和正常周围的结直肠组织从个体患者的非洲裔美国人和高加索人的起源。本研究与其他既往研究的不同之处在于，将采用多平台技术来准确评估上皮结直肠腺瘤的遗传变化和类似疾病患者的亚类，并将结果与种族/民族人群相关联。这项研究的结果应该为开发适当的临床试验提供基础知识，以预测患者临床结局中的CRC进展，这是有效治疗所必需的。

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.