Molecular Phenotype of Polyps in Serrated Polyposis Syndrome

锯齿状息肉病综合征息肉的分子表型

• 批准号: 8491617
• 负责人: RANDALL Walter BURT
• 金额: $ 19.46万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8491617
• 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

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）：每年在美国，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通常前体。锯齿状的息肉以前被认为是无害的。但是，最近的研究提供了证据，表明20-35％的结肠癌来自锯齿状息肉的子集。锯齿状的息肉分为两个主要亚型：无链锯齿状腺瘤/息肉（SSA/PS）和传统的增生息肉。 SSA/PS似乎具有发展为结肠癌的最大风险，而传统的增生息肉则被认为是良性的。一个主要的挑战是通过内窥镜检查或组织学检查将SSA/PS与传统的增生息肉区分开。此外，我们对它们发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，使用新技术定义SSA/PS的基因表达表型将导致对SSA/PS的肿瘤进展的重要见解，改善SSA/PS的诊断，并最终减少因SSA/PS而患有Colon Cancer癌症患者的数量。最初，我们将研究SSA/PS患者（锯齿状息肉病综合征）患者的极端例子。锯齿状息肉病综合征患者的结肠癌率很高，约为30-40％。这些患者及其富集的癌症风险中的众多SSA/PS为研究SSA/PS及其与结肠癌的关系提供了出色的机会。我们的研究包括可用的此类患者的最大人群之一。我们已经从这些患者和对照组中获得了SSA/PS和相邻的结肠活检标本，并应用了新的RNA分离和基因表达分析技术来研究它们。我们的方法检查了RNA聚合酶II基因表达，并具有明显增强的分辨率，以找到基因表达标记并提高我们对SSA/PS中改变的基因调节途径的了解。我们假设我们的方法和独特的患者队列将确定更准确地诊断SSA/PS的基因表达标记面板，预测其癌症风险，并能够对SSA/PS向结肠癌的进展进行机理研究。我们有一个杰出的专家团队，包括Drs。 Randy Burt（APC基因的共同发现者），Curt Hagedorn（RNA分析和生物学），Mary Bronner（GI病理学），David Nix（生物信息学）（生物信息学）和David Jones（结肠癌机制和表观遗传学），以成功地作为SSA/PS作为结肠癌的前体进行了这项研究。