CaP Metastasis Biomarkers: Validation/Genomics/Biology

CaP 转移生物标志物：验证/基因组学/生物学

基本信息

批准号：
7272019
负责人：
COLIN C COLLINS
金额：
$ 28.37万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7272019
关键词：
Age Algorithms American Antigens Apoptosis Attenuated Behavior Benign Biochemical Biological Markers Biology Biopsy Blinded Brain Brain Neoplasms Breast Candidate Disease Gene Categories Cell Line Cells Cessation of life Chromosome Mapping Clinical Clinical Oncology Clinical Trials Core Biopsy Cutaneous Data Databases Decision Making Diagnosis Disease Disease-Free Survival Distant Metastasis Doctor of Philosophy Drug Delivery Systems Drug Industry Engineering Event Extracapsular Failure Fibrous capsule of kidney Flow Cytometry Fluorescent in Situ Hybridization Freezing Gene Expression Gene Expression Profiling Gene Silencing Genes Genome Genomics Genotype Genus Capra Gleason Grade for Prostate Cancer Goals Gold Grouping Human Immunohistochemistry In Vitro Individual Laboratories Lead Liver Lung Malignant Neoplasms Malignant neoplasm of prostate Maps Measurement Measures Methods Modeling Neoplasm Metastasis Nomograms Nude Mice Numbers Oncogenes Operative Surgical Procedures Organ Outcome Ovarian PIK3CA gene PTEN gene Paraffin Embedding Pathologic Pathway interactions Patients Pattern Pharmacologic Substance Phenotype Polymerase Chain Reaction Population Postoperative Period Primary Neoplasm Probability Process Prostate Prostate-Specific Antigen Prostatic Epithelium Prostatic Neoplasms Proteins Publishing RNA Radical Prostatectomy Range Rate Recurrence Research Personnel Resolution Risk Risk Assessment Screening procedure Site Small Interfering RNA Staging Standards of Weights and Measures TGFB1 gene Testing Therapeutic Thinking Time Tissue Microarray Tissues Tumor Suppressor Genes Tumor stage Validation Variant Work base bone cell motility comparative comparative genomic hybridization cost design experience follow-up human PIK3CA protein improved in vivo instrument interest lymph nodes male men mortality novel strategies ovarian neoplasm prognostic research study small hairpin RNA therapeutic target tool tumor tumor growth tumor progression tumorigenic

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer (CaP) is diagnosed in ~ 230,000 men annually making it the most commonly diagnosed non-cutaneous cancer among American men. Moreover, approximately 30,000 men die each year from metastasis, thus there is an urgent need to understand the mechanism of metastasis. We have analyzed ~ 130 prostate tumors using array comparative genomic hybridization (aCGH). These tumors include those from 64 men at intermediate to high-risk of progression with up to 16 years clinical follow-up. Half the patients progressed biochemically (PSA) and half did not. Included amongst the tumors that recurred are 12 primary tumors that later metastasized to bone. In an independent study, the genomes of 19 organ metastases were analyzed using aCGH. Copy number profiles from the 12 primary tumors that metastasized and 19 metastases were used to detect signatures of metastasis in primary tumors. These events occur as relatively rare events in primary tumors but manifest as highly recurrent amplifications and deletions in the metastases. BAG clones at the 39 loci were required to detect the signatures of metastasis. We call these loci the genomic evaluators of metastatic CaP (GEMCaP). These findings have far reaching and indeed paradigm shifting implications for the diagnosis and treatment of CaP. We will validate the GEMCaP loci in a blinded study and compare their ability to predict recurrence to the UCSF-CAPRA and Kattan risk assessment nomograms. To focus our studies on the highest value loci we will employ comparative oncogenomics and integrate GEMCaP data with aCGH data from brain, breast, and ovarian tumors. Thus, we will test the hypothesis that markers of progression and metastasis identified using CaP metastases can predict the clinical behavior of independent primary tumor types and, moreover, may lead to broad spectrum drug targets with associated predictive biomarkers. A limited number of GEMCaP loci aberrant in multiple tumors types will be functionally analyzed in vitro and in vivo. This type of approach is essential if potential therapies discovered in academic laboratories are to be advanced to clinical oncology through the pharmaceutical industry, with the goal of eliminating death and suffering from cancer by 2015 as challenged by Dr. von Eschenbach.

描述（由申请人提供）：每年约有23万名男性诊断出前列腺癌（CAP），使其成为美国男性中最常见的非乳腺癌。此外，每年大约有30,000名男性死于转移，因此迫切需要了解转移的机制。我们使用阵列比较基因组杂交（ACGH）分析了〜130个前列腺肿瘤。这些肿瘤包括64名中级男性到高风险进展的肿瘤，最多16年的临床随访。一半的患者在生化（PSA）和一半没有进展。复发的肿瘤包括12种原发性肿瘤，后来转移到骨头。在一项独立的研究中，使用ACGH分析了19个器官转移的基因组。来自12个转移和19个转移酶的12个原发性肿瘤的拷贝数谱图检测原发性肿瘤中转移的特征。这些事件是在原发性肿瘤中相对罕见的事件，但表现为转移酶中高度复发的扩增和缺失。需要39个基因座的袋子克隆来检测转移的特征。我们称这些基因座为转移性帽（Gemcap）的基因组评估者。这些发现的到来，实际上对CAP的诊断和处理具有范式转移的影响。我们将在一项盲目的研究中验证Gemcap基因座，并将其预测复发的能力与UCSF-CAPRA和KATTAN风险评估列图进行比较。为了将研究重点放在最高价值基因座上，我们将采用比较性致癌基因组学，并将Gemcap数据与来自大脑，乳腺癌和卵巢肿瘤的ACGH数据相结合。因此，我们将测试以下假设：使用帽转移识别的进展和转移标记可以预测独立原发性肿瘤类型的临床行为，而且可能导致与相关的预测生物标志物的广谱药物靶标。在多种肿瘤类型中，有限数量的Gemcap基因座异常将在体外和体内进行功能分析。如果在学术实验室中发现的潜在疗法将通过制药行业推进临床肿瘤学，那么这种方法至关重要，目的是消除冯·埃辛巴赫（Von Eschenbach）博士在2015年消除癌症的死亡和痛苦。