Molecular Diagnosis and Prognosis in Aggressive Lymphoma

侵袭性淋巴瘤的分子诊断和预后

基本信息

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
项目类别：
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

项目摘要

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）：此申请是根据第10杆 - 126年的响应编写的，战略合作伙伴以评估癌症的签名[Specs II]（U01）。验证多分析物的诊断和预后基因特征分析以区分每个淋巴淋巴管的5个最常见的B细胞淋巴瘤。将在所有3个平台上测试基因表达（纳米结构）和定量核酸酶保护测定（高吞吐量基因组）。在第2阶段，“获胜”平台将在PCC和2个其他站点进行测试。在第2阶段，测试的基因将扩展到包括预后特征。数据将以适合提交监管审查的方式生成。与我们以前的发现工作相比，该工作是使用恐吓且仅在学术中心使用的snap冷冻组织进行的，该项目将使用固定的石蜡嵌入式组织（FFPET）使用，这些组织（FFPET）通常可以从所有活检中获得，以便具有最广泛的临床应用。 LLMPP是通过执行“金标准” GEP实验来实现这项工作的独特姿态，这些实验定义了这些淋巴瘤中的诊断和预后区别，并在同一病例中保留了匹配的FFPET块。因此，这项拟议的研究解决了将侵袭性淋巴瘤分子诊断的先前进步转化为一种新的临床范式，以进行准确的诊断，预后和治疗靶识别，这是一种至关重要的需求。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.

Diffuse large B-cell lymphoma cell-of-origin classification using the Lymph2Cx assay in the context of BCL2 and MYC expression status.

DOI：
10.3109/10428194.2015.1072767
发表时间：
2016
期刊：
Leukemia & lymphoma
影响因子：
2.6
作者：
Kendrick S;Tus K;Wright G;Jaffe ES;Rosenwald A;Campo E;Chan WC;Connors JM;Braziel RM;Ott G;Delabie J;Cook JR;Weisenburger DD;Greiner TC;Fu K;Staudt LM;Gascoyne RD;Scott DW;Rimsza LM
通讯作者：
Rimsza LM

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.

DOI：
10.1097/pas.0000000000000473
发表时间：
2015-10
期刊：
The American journal of surgical pathology
影响因子：
0
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)

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。