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）： 定义非霍奇金淋巴瘤 (NHL) 常见类别的基因表达特征已被确定，包括一些以前未识别的独特亚型。这些 NHL 的分子预测因子也已被描述。我们最近开发了一种具有 2500 多个特征的 DNA 微阵列，包括所有已知的 NHL 诊断和预后参数。我们建议使用该数组来研究 2400 个新案例，以随着研究的进展验证和完善当前以及新发现的签名和算法。这一目标的完成将为准确的诊断和预测应用提供一个强大的、具有成本效益的系统。还将开发一种可应用于石蜡包埋组织的基于定量 (Q) RT-PCR 的替代平台。它将整合来自微阵列平台的基本信息，并允许评估不是专门为微阵列分析收集的样本的关键参数，从而极大地扩展了信息的效用。有证据表明，遗传数据可以为当前基因表达衍生的预测提供额外的预测信息。我们建议获得关于弥漫性大 B 细胞淋巴瘤的全面、高分辨率的分子遗传学数据，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。由于现有的预测指标源自抗 CD20 疗法出现之前的档案病例研究，因此将在接受当前治疗方案治疗的患者中重新评估这些预测指标。将进行修改以保持预测器的准确性。这项研究不仅将验证先前定义的诊断和预后特征，还将进一步完善特征和算法，以实现更高的准确性和鲁棒性。通过将这些信息应用到 Q-RT-PCR 平台上，应用范围将得到扩展。遗传数据的纳入将增强预测能力，并通过重新评估接受当前治疗方案治疗的患者群体来更新预测能力。

项目成果

The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival.

滤泡性淋巴瘤诊断时存在 TP53 突变，可识别出疾病进展时间缩短且总体生存率较差的高危患者群体。

• DOI: 10.1182/blood-2008-05-154013
• 发表时间: 2008-10-15
• 期刊: Blood
• 影响因子: 20.3
• 作者: D. O’Shea;C. Ó'Riain;Claire F. Taylor;R. Waters;E. Carlotti;F. Macdougall;J. Gribben;A. Rosenwald;G. Ott;G. Ott;L. Rimsza;E. Smel;N. Johnson;E. Campo;T. Greiner;W. Chan;R. Gascoyne;George W. Wright;L. Staudt;T. A. Lister;J. Fitzgibbon
• 通讯作者: J. Fitzgibbon

Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.

具有和不具有t(14;18)易位的滤泡性淋巴瘤在基因表达谱和遗传改变方面有所不同。

• 发表时间: 2009-07-23
• 影响因子: 20.3
• 作者: Leich, Ellen;Salaverria, Itziar;Bea, Silvia;Zettl, Andreas;Wright, George;Moreno, Victor;Gascoyne, Randy D;Chan, Wing;Braziel, Rita M;Rimsza, Lisa M;Weisenburger, Dennis D;Delabie, Jan;Jaffe, Elaine S;Lister, Andrew;Fitzgibbon, Jude;S
• 通讯作者: S

The miR-17-92 microRNA cluster is regulated by multiple mechanisms in B-cell malignancies.

miR-17-92 microRNA 簇在 B 细胞恶性肿瘤中受到多种机制的调节。

• DOI: 10.1016/j.ajpath.2011.06.008
• 发表时间: 2011-10-01
• 期刊: The American journal of pathology
• 作者: M. Ji;E. Rao;Himabindu Ramach;rareddy;rareddy;Yulei Shen;Chunsun Jiang;Jian;Yi;A. Rizzino;W. Chan;K. Fu;T. Mckeithan
• 通讯作者: T. Mckeithan

MicroRNA profiles of t(14;18)-negative follicular lymphoma support a late germinal center B-cell phenotype.

t(14;18) 阴性滤泡性淋巴瘤的 MicroRNA 谱支持晚期生发中心 B 细胞表型。

• DOI: 10.1182/blood-2011-06-361972
• 发表时间: 2011-11-17
• 期刊: Blood
• 影响因子: 20.3
• 作者: E. Leich;A. Zamó;H. Horn;E. Haralambieva;B. Puppe;R. Gascoyne;W. Chan;R. Braziel;L. Rimsza;D. Weisenburger;J. Delabie;E. Jaffe;J. Fitzgibbon;L. Staudt;H. Mueller;M. Calaminici;E. Campo;G. Ott;Luís Hernández;A. Rosenwald
• 通讯作者: A. Rosenwald

Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma.

定量蛋白质组学揭示 miR-155 调节弥漫性大 B 细胞淋巴瘤中的 PI3K-AKT 通路。

• DOI: 10.1016/j.ajpath.2012.03.013
• 发表时间: 2012-07-01
• 期刊: The American journal of pathology
• 作者: Xin Huang;Yulei Shen;Miao Liu;Chengfeng Bi;Chunsun Jiang;J. Iqbal;T. Mckeithan;W. Chan;Shi;K. Fu
• 通讯作者: K. Fu