Biomarker Reference Laboratory

生物标志物参考实验室

基本信息

批准号：
10483360
负责人：
Jeffrey John Tosoian
金额：
$ 28.12万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10483360
关键词：
Academic Medical Centers African American African American population Biological Assay Biological Markers Biopsy COVID-19 Clinical Collaborations Communities Data Development Diagnosis Diagnostic tests ERG gene Early Detection Research Network Early Diagnosis Early treatment Foundations Future Gene Fusion Goals Guidelines Health Incidence Industry Institution Laboratories Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Michigan Mission Molecular Mutation New York PSA screening Pathology Population Populations at Risk Procedures Prostate Prostate-Specific Antigen Prostatic Diseases Quality Control RNA Splicing Race Reproducibility Research Resources Role Running Sampling Standardization TMPRSS2 gene Testing Texas Tissues Training Transcript Translating Translations Underrepresented Populations Universities Untranslated RNA Urine Validation Variant Virginia Work antigen test base cancer biomarkers candidate marker caucasian American circular RNA clinical application clinical diagnostics clinically significant cohort cost curative treatments detection test diagnostic platform diagnostic tool experience high risk industry partner insertion/deletion mutation medical schools men molecular subtypes mortality multidisciplinary next generation sequencing novel novel diagnostics novel marker personalized risk prediction predictive modeling research clinical testing serum PSA shared decision making specific biomarkers success tool transcriptome sequencing transcriptomics urinary

Academic Medical Centers African American African American population Biological Assay Biological Markers Biopsy COVID-19 Clinical Collaborations Communities Data Development Diagnosis Diagnostic tests ERG gene Early Detection Research Network Early Diagnosis Early treatment Foundations Future Gene Fusion Goals Guidelines Health Incidence Industry Institution Laboratories Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Michigan Mission Molecular Mutation New York PSA screening Pathology Population Populations at Risk Procedures Prostate Prostate-Specific Antigen Prostatic Diseases Quality Control RNA Splicing Race Reproducibility Research Resources Role Running Sampling Standardization TMPRSS2 gene Testing Texas Tissues Training Transcript Translating Translations Underrepresented Populations Universities Untranslated RNA Urine Validation Variant Virginia Work antigen test base cancer biomarkers candidate marker caucasian American circular RNA clinical application clinical diagnostics clinically significant cohort cost curative treatments detection test diagnostic platform diagnostic tool experience high risk industry partner insertion/deletion mutation medical schools men molecular subtypes mortality multidisciplinary next generation sequencing novel novel diagnostics novel marker personalized risk prediction predictive modeling research clinical testing serum PSA shared decision making specific biomarkers success tool transcriptome sequencing transcriptomics urinary

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项目摘要

Project Summary/Abstract This application proposes the formation of the Michigan-Vanderbilt University Medical Center (VUMC) EDRN Biomarker Characterization Center (BCC). This BCC represents a collaborative, multi-disciplinary team of academic (University of Michigan (U-M) and VUMC) and industry (LynxDx) partners focused on discovering, developing, and scaling clinical-grade assays for the early detection of aggressive prostate cancer. Through previous EDRN efforts, our team characterized multiple important prostate cancer biomarkers, most notably the TMPRSS2-ETS gene fusions. Through collaboration with an EDRN Clinical Validation Center (CVC; Dr. Sanda PI), we developed, validated, and clinically implemented MyProstateScore (MPS), an early detection test incorporating urine quantification of two prostate cancer-specific transcripts—the TMPRSS2:ERG gene fusion and the long non-coding RNA (lncRNA) PCA3. Introduced in our CLIA laboratory, MPS informs shared decision making after PSA testing based on individualized risk predictions of aggressive prostate cancer on biopsy. Here, pairing the cancer-specific components of the MPS test with recent discovery of high-grade cancer-specific biomarkers, we outline the development, optimization, and clinical validation of the next generation of diagnostic tests – capable of reliably, selectively detecting potentially lethal cancers that stand to benefit from early curative treatment. Our Biomarker Developmental Laboratory (BDL) will employ the experimental platform, MPS-SEQ, for capture RNA-seq analysis of urine samples to detect aggressive prostate cancer transcripts, lncRNAs, circular RNAs, fusion transcripts, mutations, indels, and splice variants. Our Biomarker Reference Laboratory (BRL) will in parallel develop a clinical grade urine assay, MPS-50, for the multiplex QPCR analysis of up to 50 amplicons. While the first 50 amplicons of MPS-50 have already been nominated, future improvements of the assay content and platform will be informed by work carried out in our BDL. To fuel these studies, our BCC has identified urine biospecimen cohorts collected under rigorous standard operating procedures in compliance with PRoBE criteria including the Michigan Prostate SPORE, Emory University, the Center for Prostate Disease Research, University of Texas San Antonio Health, Eastern Virginia Medical School, and VUMC/Meharry Medical College. The overall Aims of this BCC serve to develop, assess, and optimize MPS-SEQ and MPS-50 for identifying high-grade prostate cancer in diverse at-risk populations. Our BRL will also focus on standardizing clinically-validated biomarker assays for consistent and reliable use in accordance with CLIA/CAP guidelines at the U-M Center for Translational Pathology in order to facilitate network consortium studies and at LynxDx in order to scale, commercialize, and obtain FDA approvals. As recognized by the EDRN, novel biomarkers specific for aggressive prostate cancer are urgently needed. Importantly, our mission and efforts extend beyond our BCC and prostate cancer, as we actively participate in the EDRN biomarker community and support continued collaborative efforts with other BCCs and CVCs to advance the overall EDRN mission.

项目摘要/摘要该申请提出了密歇根州 - 弗兰德比尔特大学医学中心（VUMC）EDRN的形成生物标志物特征中心（BCC）。该BCC代表了一个合作的，多学科的团队学术（密歇根大学（U-M）和VUMC）和行业（Lynxdx）合作伙伴致力于发现，开发和缩放临床级测定，以早日检测侵袭性前列腺癌。通过以前的EDRN努力，我们的团队表征了多个重要的前列腺癌生物标志物，最著名的是 TMPRSS2-ET基因融合。通过与EDRN临床验证中心的合作（CVC； Sanda博士 PI），我们开发，验证和临床实施了MyProstateCore（MPS），这是一个早期检测测试纳入两个前列腺癌特异性转录本的尿液定量-TMPRSS2：ERG基因融合以及长的非编码RNA（LNCRNA）PCA3。国会议员在我们的CLIA实验室中引入了共同的决定根据活检对侵袭性前列腺癌的个性化风险预测进行PSA测试后进行。这里，将MPS测试的癌症特异性组成部分与最近发现的高级癌症特异生物标志物，我们概述了下一代诊断的开发，优化和临床验证测试 - 能够可靠，有选择地检测可能受益于早期治疗的潜在致命癌治疗。我们的生物标志物发展实验室（BDL）将采用实验平台MPS-Seq，为了捕获尿液样品的RNA-seq分析，以检测攻击性前列腺癌转录本LNCRNA，圆形RNA，融合转录本，突变，indels和剪接变体。我们的生物标志物参考实验室（BRL）将并行开发临床级尿液测定MPS-50，以进行多达50的多重QPCR分析尽管MPS-50的前50个扩增子已经提名，但未来的改进测定内容和平台将通过我们的BDL中进行的工作告知。为了促进这些研究，我们的BCC有确定了根据严格的标准操作程序收集的尿液生物循环群体探测标准包括密歇根前列腺孢子，埃默里大学，前列腺疾病中心德克萨斯大学圣安东尼奥大学，东弗吉尼亚医学院和VUMC/Meharry研究医学院。该BCC的总体目标是开发，评估和优化MPS-Seq和MPS-50 用于鉴定潜水风险种群中的高级前列腺癌。我们的BRL也将专注于标准化根据CLIA/CAP指南，临床验证的生物标志物测定法 U-M转化病理中心，以促进网络联盟研究和在lynxdx中为了扩展，商业化并获得FDA批准。正如EDRN所认可的，新颖的生物标志物特定于迫切需要前列腺癌。重要的是，我们的使命和努力超出了BCC 和前列腺癌，随着我们积极参与EDRN生物标志物社区并继续与其他BCC和CVC的合作努力，以推进EDRN的整体任务。