Molecular Diagnosis and Prognosis in Aggressive Lymphoma

侵袭性淋巴瘤的分子诊断和预后

• 批准号: 9191003
• 负责人: Lisa Rimsza
• 金额: $ 84.18万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9191003
• 关键词: Molecular; Diagnosis; Prognosis; Aggressive; Lymphoma

DESCRIPTION (provided by applicant): This application is written in response to PAR-10-126, Strategic Partnering to Evaluate of Cancer Signatures [SPECS II] (U01)." The proposed project focuses on translating our previously discovery-oriented gene expression signatures into laboratory tests for lymphoma clinical trials and patient care. Our research consortium, the Lymphoma and Leukemia Molecular Profiling Project (LLMPP) will design and validate a multi-analyte diagnostic and prognostic gene signature assay to differentiate the 5 most common aggressive B cell non-Hodgkin lymphomas. Each lymphoma subtype will then be further classified into prognostic groups. Three methods of gene expression profiling with demonstrated utility in our feasibility testing will be rigorously evaluated including high density oligonucleotide arrays (Affymetrix), direct multiplexed measurement of gene expression (Nanostring), and quantitative nuclease protection assay (High Throughput Genomics). In Phase 1 diagnostic genes will be tested at all 3 platforms will be compared simultaneously at the Patient Characterization Center (PCC) at NCI-Frederick, operated by SAIC-Frederick and a second academic study site. In Phase 2, the "winning" platform will be tested at the PCC and 2 additional sites. In Phase 2, tested genes will be expanded to include prognostic signatures. Data will be generated in such a way as to be appropriate for submission for regulatory review. As opposed to our previous discovery work that was performed with snap frozen tissues which are scare and only available at academic centers, this project will use formalin fixed, paraffin embedded tissues (FFPET), which are routinely available from all biopsies, in order to have the broadest clinical application. The LLMPP is uniquely posed to accomplish this work by virtue of having performed the "gold standard" GEP experiments that define the diagnostic and prognostic distinctions in these lymphomas as well as holding matching FFPET blocks from the same cases. Hence, this proposed research addresses a critical unmet need to translate previous advances in the molecular diagnosis of aggressive lymphomas into a new clinical paradigm for accurate diagnosis, prognosis, and therapeutic target identification.

描述（由申请人提供）：本申请是根据PAR-10-126，癌症特征评价战略合作[SPECS II]（U 01）编写的。“拟议的项目重点是将我们以前以发现为导向的基因表达特征转化为淋巴瘤临床试验和患者护理的实验室测试。我们的研究联盟，淋巴瘤和白血病分子特征项目（LLMPP）将设计和验证一种多分析物诊断和预后基因签名检测，以区分5种最常见的侵袭性B细胞非霍奇金淋巴瘤。然后将每种淋巴瘤亚型进一步分类为预后组。将严格评估在我们的可行性测试中具有已证明效用的三种基因表达谱分析方法，包括高密度寡核苷酸阵列（Affytron）、基因表达的直接多重测量（Nanostring）和定量核酸酶保护测定（High Troput Genomics）。在第1阶段，诊断基因将在所有3个平台上进行检测，并将在NCI-Frederick的患者表征中心（PCC）同时进行比较，该中心由SAIC-Frederick和第二个学术研究中心运营。在第二阶段，“获胜”平台将在PCC和另外两个站点进行测试。在第2阶段，测试的基因将被扩展到包括预后标志。将以适当的方式生成数据，以便提交监管审查。与我们之前使用速冻组织进行的发现工作相反，速冻组织很少并且仅在学术中心可用，该项目将使用福尔马林固定的石蜡包埋组织（FFPET），其通常可从所有活检中获得，以便具有最广泛的临床应用。LLMPP是唯一提出来完成这项工作，凭借已经进行了“金标准”GEP实验，定义这些淋巴瘤的诊断和预后的区别，以及持有匹配的FFPET块从相同的情况下。因此，这项拟议的研究解决了一个关键的未满足的需要，将以前在侵袭性淋巴瘤的分子诊断方面的进展转化为一种新的临床范式，用于准确的诊断，预后和治疗靶点鉴定。

项目成果

BCL2 antibodies targeted at different epitopes detect varying levels of protein expression and correlate with frequent gene amplification in diffuse large B-cell lymphoma.

• DOI: 10.1016/j.humpath.2014.06.005
• 发表时间: 2014-10
• 期刊: HUMAN PATHOLOGY
• 影响因子: 3.3
• 作者: Kendrick, Samantha L.;Redd, Lucas;Muranyi, Andrea;Henricksen, Leigh A.;Stanislaw, Stacey;Smith, Lynette M.;Perry, Anamarija M.;Fu, Kai;Weisenburger, Dennis D.;Rosenwald, Andreas;Ott, German;Gascoyne, Randy D.;Jaffe, Elaine S.;Campo, Elias;Delabie, Jan;Braziel, Rita M.;Cook, James R.;Tubbs, Raymond R.;Staudt, Louis M.;Chan, Wing Chung;Steidl, Christian;Grogan, Thomas M.;Rimsza, Lisa M.
• 通讯作者: Rimsza, Lisa M.

Incorporation of Digital Gene Expression Profiling for Cell-of-Origin Determination (Lymph2Cx Testing) into the Routine Work-Up of Diffuse Large B-Cell Lymphoma.

• DOI: 10.1007/s12308-019-00344-0
• 发表时间: 2019-03
• 期刊: Journal of hematopathology
• 影响因子: 0.6
• 作者: Robetorye RS;Ramsower CA;Rosenthal AC;Yip TK;Wendel Spiczka AJ;Glinsmann-Gibson BJ;Rimsza LM
• 通讯作者: Rimsza LM

Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling.

通过基因表达分析鉴定在非中服，在非中伴部位鉴定。

• DOI: 10.1097/pas.0000000000000473
• 发表时间: 2015-10
• 期刊: The American journal of surgical pathology
• 作者: Yuan J;Wright G;Rosenwald A;Steidl C;Gascoyne RD;Connors JM;Mottok A;Weisenburger DD;Greiner TC;Fu K;Smith L;Rimsza LM;Jaffe ES;Campo E;Martinez A;Delabie J;Braziel RM;Cook JR;Ott G;Vose JM;Staudt LM;Chan WC;Lymphoma Leukemia Molecular Profiling Project (LLMPP)
• 通讯作者: Lymphoma Leukemia Molecular Profiling Project (LLMPP)

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

• DOI: 10.1056/nejmoa1801445
• 发表时间: 2018-04-12
• 期刊: The New England journal of medicine
• 作者: Schmitz R;Wright GW;Huang DW;Johnson CA;Phelan JD;Wang JQ;Roulland S;Kasbekar M;Young RM;Shaffer AL;Hodson DJ;Xiao W;Yu X;Yang Y;Zhao H;Xu W;Liu X;Zhou B;Du W;Chan WC;Jaffe ES;Gascoyne RD;Connors JM;Campo E;Lopez-Guillermo A;Rosenwald A;Ott G;Delabie J;Rimsza LM;Tay Kuang Wei K;Zelenetz AD;Leonard JP;Bartlett NL;Tran B;Shetty J;Zhao Y;Soppet DR;Pittaluga S;Wilson WH;Staudt LM
• 通讯作者: Staudt LM

Diffuse Large B-cell Lymphoma Classification Tied Up Nicely with a "String".

弥漫性大 B 细胞淋巴瘤分类与“绳子”紧密相连。

• DOI: 10.1158/1078-0432.ccr-15-0253
• 发表时间: 2015
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Rimsza,LisaM