Tissue Print Micropeels for Molecular Profiling Cancer

用于癌症分子分析的组织打印显微剥离术

• 批准号: 6862319
• 负责人: SANDRA M GASTON
• 金额: $ 14.62万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6862319
• 关键词: breast neoplasms; clinical research; histopathology; human data; human tissue; molecular oncology; polymerase chain reaction; prostate neoplasms; technology /technique development; tissue /cell preparation

DESCRIPTION (provided by applicant): Molecular profiling has emerged as an important strategy for identifying marker "signatures" associated with the biological changes that characterize specific cancers. To realize the full potential of the wealth of new biomarker information, it is essential to develop strategies for profiling human tissue and tumor specimens that are workable in a clinical setting. Clinical specimens are heterogeneous, and tissue heterogeneity is one of the major sources of complexity that must be addressed in the application of molecular profiling to the analysis of human cancers. We have developed a set of novel "tissue print" techniques that allow us to profile the molecular markers over extended areas of human tissue and tumor samples without damaging the specimen. We first applied our new tissue print techniques in the profiling of protein markers associated with capsular invasion in radical prostatectomy specimens. More recently, we have discovered that, during tissue print collection, we can peel a layer of cells off of the specimen and that this process does not cause detectable tissue damage (as determined by surgical pathologists), and thus does not interfere with routine clinical surgical pathology. We have also shown that the cells collected in the tissue print "micropeel" are adequate for PCR and quantitative rt-PCR analysis, allowing us to score multiple molecular markers and assemble the results in "tiling patterns" corresponding to the specimen surface. In the project outlined in this proposal, we will work closely with the research and development team at Qiagen Inc. to optimize the yield of mRNA and DNA from our tissue print micropeels collected from human prostate and breast tissue/tumors specimens. We will then develop a proof-of-principle pilot application of the tissue-print micropeel sampling technique for prostate needle biopsies, one of the classes of specimens that must be conserved intact for clinical diagnosis. Our long term goal is to utilize tissue print techniques in the clinical setting to simplify the process of obtaining an adequate representation of human cancers in biopsies and surgical specimens, and to develop protocols for this tissue sampling platform to support both proteomic analysis and PCR-based DNA and mRNA profiling techniques. In addition to facilitating basic and translational research, the tissue-printing platform can also be utilized as a tool for dedicated clinical applications, to provide "molecular sections" of extended areas of the specimen when the marker profile is itself of potential diagnostic importance.

描述（由申请人提供）：分子谱分析已成为识别与表征特定癌症的生物学变化相关的标记物“特征”的重要策略。为了充分发挥大量新生物标志物信息的潜力，必须制定在临床环境中可行的人体组织和肿瘤标本分析策略。临床标本是异质的，组织异质性是复杂性的主要来源之一，在将分子谱分析应用于人类癌症分析时必须解决这一问题。我们开发了一套新颖的“组织打印”技术，使我们能够在人体组织和肿瘤样本的扩展区域上分析分子标记，而不会损坏样本。我们首先将新的组织打印技术应用于与根治性前列腺切除术标本中包膜侵袭相关的蛋白质标记物的分析。最近，我们发现，在组织打印收集过程中，我们可以从样本上剥离一层细胞，并且此过程不会造成可检测到的组织损伤（由外科病理学家确定），因此不会干扰常规临床外科病理学。我们还表明，在组织印迹“micropeel”中收集的细胞足以进行 PCR 和定量 rt-PCR 分析，使我们能够对多个分子标记进行评分，并将结果组装成与样本表面相对应的“平铺图案”。 在本提案概述的项目中，我们将与 Qiagen Inc. 的研发团队密切合作，优化从人类前列腺和乳腺组织/肿瘤标本中收集的组织打印微剥离中的 mRNA 和 DNA 产量。然后，我们将开发一种用于前列腺针活检的组织打印微剥离采样技术的原理验证试点应用，这是临床诊断必须完整保存的样本之一。我们的长期目标是在临床环境中利用组织打印技术来简化在活检和手术标本中获得人类癌症的充分代表性的过程，并为该组织采样平台开发协议以支持蛋白质组分析和基于 PCR 的分析DNA 和 mRNA 分析技术。除了促进基础和转化研究之外，组织打印平台还可以用作专用临床应用的工具，当标记物轮廓本身具有潜在的诊断重要性时，提供样本扩展区域的“分子切片”。