Molecular Phenotype of Polyps in Serrated Polyposis Syndrome

锯齿状息肉病综合征息肉的分子表型

基本信息

批准号：
8752300
负责人：
CURT H. HAGEDORN
金额：
$ 15.56万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8752300
关键词：
APC gene Accounting Adenomatous Polyps Attention Automobile Driving Benign Bioinformatics Biology Biometry Biopsy Specimen Caliber Cancer Etiology Cessation of life Clinical Colon Colon Carcinoma Colonic Polyps Colonoscopy DNA Polymerase II Data Set Diagnosis Diagnostic Endoscopic Biopsy Epigenetic Process Follow-Up Studies Future Gene Expression Gene Expression Profile Gene Expression Profiling General Population Genes Genomics Goals Hyperplasia Hyperplastic Polyp Incidence Institution Knowledge Laboratories Lead Lesion Malignant Neoplasms Mining Molecular Molecular Diagnostic Testing Molecular Profiling Mucous Membrane Outcome Pathology Pathway interactions Patients Phenotype Polyps Prevention strategy Problem Solving Prognostic Marker RNA RNA Caps RNA Polymerase II RNA Sequence Analysis RNA Sequences RNA analysis Regulatory Pathway Resolution Risk Risk Marker Sampling Serrated Adenoma Sigmoid colon Syndrome Technology Testing Transcript Validation Woman base cancer prevention cancer risk cancer therapy cohort design follow-up high risk improved insight men molecular marker molecular phenotype new technology novel strategies polyposis prevent prognostic public health relevance screening tumor progression validation studies

项目摘要

DESCRIPTION (provided by applicant): Over 50,000 people die from colon cancer each year in the USA, making it the second leading cause of cancer death for men and women alike. Colon polyps are the usual precursors of colon cancer. Serrated polyps, which occur at a high incidence (20-30%) in the general population, were previously considered harmless. However, recent studies provide evidence that 20-35% of colon cancers arise from a subset of serrated polyps. Serrated polyps are divided into two main subtypes: sessile serrated adenomas/polyps (SSA/Ps) and traditional hyperplastic polyps. SSA/Ps appear to have the greatest risk of progressing to colon cancer whereas traditional hyperplastic polyps are considered benign. A major challenge is differentiating SSA/Ps from traditional hyperplastic polyps by endoscopic or histological examination. Moreover, we know little about their mechanism of progression to colon cancer. We predict that using new technologies to define the gene expression phenotype of SSA/Ps, as compared to traditional hyperplastic, adenomatous polyps and controls, will lead to important insights into the neoplastic progression of SSA/Ps, improve the diagnosis of SSA/Ps and eventually decrease the number of patients suffering from colon cancer due to SSA/Ps. We initially will study an extreme example of patients with SSA/Ps, the serrated polyposis syndrome. Patients with the serrated polyposis syndrome have a high rate of colon cancer, approximately 30-40%. The numerous SSA/Ps in these patients and their enriched cancer risk provide an outstanding opportunity to study SSA/Ps and their relationship to colon cancer. Our study includes one of the largest cohorts of such patients available. We have already obtained SSA/Ps and adjacent colon biopsy specimens from these patients and controls and have applied new RNA isolation and gene expression profiling technologies to study them. Our approach examines RNA polymerase II gene expression, with a markedly enhanced resolution, to find gene expression markers and advance our knowledge of the gene regulatory pathways altered in SSA/Ps. We hypothesize that our approach and unique patient cohort will identify panels of gene expression markers that more accurately diagnose SSA/Ps, predict their cancer risk and enable mechanistic studies of the progression of SSA/Ps to colon cancer. We have an outstanding team of experts, including Drs. Randy Burt (co-discoverer of the APC gene), Curt Hagedorn (RNA analysis and biology), Mary Bronner (GI pathology), David Nix (bioinformatics) and David Jones (colon cancer mechanisms and epigenetics) to successfully conduct this study of SSA/Ps as precursors of colon cancer.

描述（由申请人提供）：在美国，每年有超过 50,000 人死于结肠癌，使其成为男性和女性癌症死亡的第二大原因。结肠息肉是结肠癌的常见前兆。锯齿状息肉在一般人群中发生率很高（20-30%），以前被认为是无害的。然而，最近的研究提供的证据表明，20-35% 的结肠癌源自锯齿状息肉的子集。锯齿状息肉分为两种主要亚型：无蒂锯齿状腺瘤/息肉（SSA/Ps）和传统增生性息肉。 SSA/P 似乎进展为结肠癌的风险最大，而传统的增生性息肉被认为是良性的。一个主要挑战是通过内窥镜或组织学检查区分 SSA/P 与传统的增生性息肉。此外，我们对其进展为结肠癌的机制知之甚少。我们预测，与传统的增生性、腺瘤性息肉和对照相比，使用新技术来定义 SSA/Ps 的基因表达表型，将为了解 SSA/Ps 的肿瘤进展提供重要见解，改善 SSA/Ps 的诊断和治疗。最终减少因SSA/Ps而患结肠癌的患者数量。我们首先将研究 SSA/P 患者的一个极端例子，即锯齿状息肉病综合征。锯齿状息肉病综合征患者患结肠癌的几率很高，约为 30-40%。这些患者中大量的 SSA/P 及其增加的癌症风险为研究 SSA/P 及其与结肠癌的关系提供了绝佳的机会。我们的研究包括此类患者的最大队列之一。我们已经从这些患者和对照中获得了 SSA/P 和邻近的结肠活检标本，并应用了新的 RNA 分离和基因表达谱技术来研究它们。我们的方法以显着增强的分辨率检查 RNA 聚合酶 II 基因表达，以找到基因表达标记并增进我们对 SSA/P 中改变的基因调控途径的了解。我们假设我们的方法和独特的患者队列将识别基因表达标记物组，从而更准确地诊断 SSA/P、预测其癌症风险并能够对 SSA/P 进展为结肠癌的机制研究。我们拥有一支优秀的专家团队，其中包括博士。 Randy Burt（APC 基因的共同发现者）、Curt Hgedorn（RNA 分析和生物学）、Mary Bronner（胃肠道病理学）、David Nix（生物信息学）和 David Jones（结肠癌机制和表观遗传学）成功开展了这项 SSA 研究/Ps 作为结肠癌的前兆。