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）：

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

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

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.

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.

Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor.

• DOI: 10.1016/j.bbrc.2008.07.116
• 发表时间: 2008-10-17
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Shen, Yulei;Ge, Baosheng;Ramachandrareddy, Himabindu;McKeithan, Timothy;Chan, Wing C.
• 通讯作者: Chan, Wing C.