Molecular Signatures to Improve Diagnosis and Outcome Pr

改善诊断和结果的分子特征

• 批准号: 7913564
• 负责人: Wing C. Chan
• 金额: $ 36.93万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7913564
• 关键词: Algorithms; B-Cell NonHodgkins Lymphoma; Biological Assay; Case Series; Categories; Classification; Clinical; Clinical Data; DNA; DNA Microarray Chip; Data; Diagnosis; Diagnostic; Disease; Evaluation; Formalin; Gene Expression; Gene Expression Profile; Genetic; Genetic Determinism; Genetic Markers; Genetic Models; Genetic Transcription; Grant; Lymphoma; MS4A1 gene; Microarray Analysis; Minor; Modeling; Modification; Molecular; Molecular Genetics; Molecular Profiling; Non-Hodgkin' s Lymphoma; Outcome; Paraffin Embedding; Patients; Polymerase Chain Reaction; Predictive Value; Prognostic Marker; Publishing; Research Personnel; Resolution; Reverse Transcription; Sampling; Specimen; Subgroup; System; Testing; Therapeutic; Time; Tissue Embedding; Tissues; Training; Treatment Protocols; Update; Validation; base; cohort; comparative genomic hybridization; cost; design; follow-up; improved; large cell Diffuse non-Hodgkin' s lymphoma; novel therapeutics; prognostic; programs

DESCRIPTION (provided by applicant): Gene expression signatures that define the common categories of non-Hodgkin's lymphoma (NHL) have been identified, including some unique subtypes not recognized previously. Molecular prognosticators for these NHLs have also been described. We have recently developed a DNA microarray with over 2500 features, including all known diagnostic and prognostic parameters for NHL. We propose to use this array to study 2400 new cases to validate and refine current as well as newly discovered signatures and algorithms as the study progresses. Completion of this aim will provide a robust, cost-effective system for accurate diagnostic and prognostic applications. An alternative, quantitive(Q) RT-PCR based platform that can be applied to paraffin-embedded tissue will also be developed. It will incorporate the essential information from of the microarray platform and allow the assessment of critical parameters in specimens not specifically collected for microarray analysis, hence greatly expanding the utility of the information. There is evidence that genetic data may provide additional prognostic information to the current gene expression-derived prognosticators. We propose to obtain comprehensive, high-resolution molecular genetic data on diffuse large B-cell lymphoma to examine if the combination of genetic and gene expression parameters will improve the current prognostic model. Since existing prognosticators were derived from the study of archival cases prior to the availablility of anti-CD20 therapy, they will be re-evaluated in patients treated with current therapeutic regimens. Modifications will be made to maintain the accuracy of the prognosticators. This study will not only validate previously-defined diagnostic and prognostic signatures, but will further refine the signatures and algorithms for higher accuracy and robustness. The range of application will be expanded by adapting the information to a Q-RT-PCR platform. Prognosticators will be enhanced by the incorporation of genetic data, and updated by a re-evaluation of cohorts of patients treated with current therapeutic regimens.

描述（由申请人提供）： 已经确定了定义非霍奇金淋巴瘤（NHL）常见类别的基因表达特征，其中包括先前未识别的一些独特的亚型。这些NHL的分子预后也已经描述了。我们最近开发了一个具有2500多个功能的DNA微阵列，包括所有已知的NHL诊断和预后参数。我们建议使用此阵列研究2400例新病例，以验证和完善当前的速度以及新发现的特征和算法，随着研究的进行。此目标的完成将为准确的诊断和预后应用提供强大的，具有成本效益的系统。还将开发一个可应用于石蜡包埋的组织的替代，定量（Q）RT-PCR的平台。它将结合微阵列平台的基本信息，并允许评估未针对微阵列分析的标本中的关键参数，从而大大扩展了信息的实用性。有证据表明，遗传数据可能会为当前基因表达衍生的预后剂提供其他预后信息。我们建议在弥漫性大B细胞淋巴瘤上获得全面的高分辨率分子遗传数据，以检查遗传和基因表达参数的组合是否会改善当前的预后模型。由于现有的预后剂来自抗CD20治疗的档案案例的研究，因此将在接受当前治疗方案治疗的患者中重新评估它们。将进行修改以保持预后剂的准确性。这项研究不仅将验证先前定义的诊断和预后特征，而且还将进一步完善签名和算法，以提高准确性和鲁棒性。通过将信息调整为Q-RT-PCR平台，将扩展应用程序范围。通过合并遗传数据将增强预后剂，并通过重新评估接受当前治疗方案治疗的患者来进行更新。

项目成果

Genome wide DNA-profiling of HIV-related B-cell lymphomas.

• DOI: 10.1111/j.1365-2141.2009.07943.x
• 发表时间: 2010-01
• 期刊: British journal of haematology
• 影响因子: 6.5
• 作者: Capello D;Scandurra M;Poretti G;Rancoita PM;Mian M;Gloghini A;Deambrogi C;Martini M;Rossi D;Greiner TC;Chan WC;Ponzoni M;Moreno SM;Piris MA;Canzonieri V;Spina M;Tirelli U;Inghirami G;Rinaldi A;Zucca E;Favera RD;Cavalli F;Larocca LM;Kwee I;Carbone A;Gaidano G;Bertoni F
• 通讯作者: Bertoni F

Oncogenically active MYD88 mutations in human lymphoma.

• DOI: 10.1038/nature09671
• 发表时间: 2011-02-03
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Ngo, Vu N.;Young, Ryan M.;Schmitz, Roland;Jhavar, Sameer;Xiao, Wenming;Lim, Kian-Huat;Kohlhammer, Holger;Xu, Weihong;Yang, Yandan;Zhao, Hong;Shaffer, Arthur L.;Romesser, Paul;Wright, George;Powell, John;Rosenwald, Andreas;Muller-Hermelink, Hans Konrad;Ott, German;Gascoyne, Randy D.;Connors, Joseph M.;Rimsza, Lisa M.;Campo, Elias;Jaffe, Elaine S.;Delabie, Jan;Smeland, Erlend B.;Fisher, Richard I.;Braziel, Rita M.;Tubbs, Raymond R.;Cook, J. R.;Weisenburger, Denny D.;Chan, Wing C.;Staudt, Louis M.
• 通讯作者: Staudt, Louis M.

Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.

• DOI: 10.1056/nejmoa0905680
• 发表时间: 2010-03-11
• 期刊: The New England journal of medicine
• 作者: Steidl C;Lee T;Shah SP;Farinha P;Han G;Nayar T;Delaney A;Jones SJ;Iqbal J;Weisenburger DD;Bast MA;Rosenwald A;Muller-Hermelink HK;Rimsza LM;Campo E;Delabie J;Braziel RM;Cook JR;Tubbs RR;Jaffe ES;Lenz G;Connors JM;Staudt LM;Chan WC;Gascoyne RD
• 通讯作者: Gascoyne RD

Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics.

• DOI: 10.1038/nature11378
• 发表时间: 2012-10-04
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Schmitz, Roland;Young, Ryan M.;Ceribelli, Michele;Jhavar, Sameer;Xiao, Wenming;Zhang, Meili;Wright, George;Shaffer, Arthur L.;Hodson, Daniel J.;Buras, Eric;Liu, Xuelu;Powell, John;Yang, Yandan;Xu, Weihong;Zhao, Hong;Kohlhammer, Holger;Rosenwald, Andreas;Kluin, Philip;Mueller-Hermelink, Hans Konrad;Ott, German;Gascoyne, Randy D.;Connors, Joseph M.;Rimsza, Lisa M.;Campo, Elias;Jaffe, Elaine S.;Delabie, Jan;Smeland, Erlend B.;Ogwang, Martin D.;Reynolds, Steven J.;Fisher, Richard I.;Braziel, Rita M.;Tubbs, Raymond R.;Cook, James R.;Weisenburger, Dennis D.;Chan, Wing C.;Pittaluga, Stefania;Wilson, Wyndham;Waldmann, Thomas A.;Rowe, Martin;Mbulaiteye, Sam M.;Rickinson, Alan B.;Staudt, Louis M.
• 通讯作者: Staudt, Louis M.

Tissue microarray in a subset of South African patients with DLBCL.

南非 DLBCL 患者亚组的组织微阵列。

• DOI: 10.1016/j.transci.2013.07.013
• 发表时间: 2013
• 期刊: Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis
• 作者: Sissolak,Gerhard;Wood,Lucille;Smith,Lynette;Chan,JohnWingC;Armitage,James;Jacobs,Peter
• 通讯作者: Jacobs,Peter