Pathway activation patterns in diffuse large B-cell lymphomas

被引：0
作者：
S Bentink
S Wessendorf
C Schwaenen
M Rosolowski
W Klapper
A Rosenwald
G Ott
A H Banham
H Berger
A C Feller
M-L Hansmann
D Hasenclever
M Hummel
D Lenze
P Möller
B Stuerzenhofecker
M Loeffler
L Truemper
H Stein
R Siebert
R Spang
机构：
[1] Institute of Functional Genomics,Nuffield Department of Clinical Laboratory Sciences
[2] University of Regensburg,Department of Hematology and Oncology
[3] Cytogenetic and Molecular Diagnostics,Department of Clinical Pathology
[4] Internal Medicine III,undefined
[5] University Hospital Ulm,undefined
[6] Institute for Medical Informatics,undefined
[7] Statistics and Epidemiology,undefined
[8] University of Leipzig,undefined
[9] Institute of Hematopathology,undefined
[10] University Hospital Schleswig-Holstein,undefined
[11] Christian-Albrechts University Kiel,undefined
[12] Institute of Pathology,undefined
[13] University of Würzburg,undefined
[14] University of Oxford,undefined
[15] Institute of Pathology,undefined
[16] University Hospital Schleswig-Holstein,undefined
[17] Institute of Pathology,undefined
[18] University Hospital Frankfurt,undefined
[19] Institute of Pathology,undefined
[20] Campus Benjamin Franklin,undefined
[21] Charité–Universitätsmedizin Berlin,undefined
[22] Institute of Pathology,undefined
[23] University Hospital Ulm,undefined
[24] Georg-August University Göttingen,undefined
[25] Institute of Human Genetics,undefined
[26] University Hospital Schleswig-Holstein,undefined
[27] Christian-Albrechts University Kiel,undefined
[28] Robert-Bosch-Krankenhaus,undefined
来源：
Leukemia | 2008年 / 22卷
关键词：
lymphoma; oncogenic pathways; transcriptional modules; cancer;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Deregulation of cell signaling pathways controlling cell growth and cell survival is a common feature of all cancers. Although a core repertoire of oncogenic mechanisms is widely conserved between various malignancies, the constellation of pathway activities can vary even in patients with the same malignant disease. Modern molecularly targeted cancer drugs intervene in cell signaling compensating for pathway deregulation. Hence characterizing tumors with respect to pathway activation will become crucial for treatment decisions. Here we have used semi-supervised machine learning methodology to generate signatures of eight oncogene-inducible pathways, which are conserved across epithelial and lymphoid tissues. We combined them to patterns of pathway activity called PAPs for pathway activation patterns and searched for them in 220 morphologically, immunohistochemically and genetically well-characterized mature aggressive B-cell lymphomas including 134 cases with clinical data available. Besides Burkitt lymphoma, which was characterized by a unique pattern, the PAPs identified four distinct groups of mature aggressive B-cell lymphomas across independent gene expression studies with distinct biological characteristics, genetic aberrations and prognosis. We confirmed our findings through cross-platform analysis in an independent data set of 303 mature aggressive B-cell lymphomas.
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页码：1746 / 1754
页数：8
相关论文
共 121 条
[1]  
Bild AH(2006)Oncogenic pathway signatures in human cancers as a guide to targeted therapies Nature 439 353-357
[2]  
Yao G(2001)Predicting the clinical status of human breast cancer by using gene expression profiles Proc Natl Acad Sci USA 98 11462-11467
[3]  
Chang JT(2000)Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling Nature 403 503-511
[4]  
Wang Q(2006)Molecular diagnosis of Burkitt's lymphoma N Engl J Med 354 2431-2442
[5]  
Potti A(2006)A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling N Engl J Med 354 2419-2430
[6]  
Chasse D(2005)Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response Blood 105 1851-1861
[7]  
West M(2002)The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma N Engl J Med 346 1937-1947
[8]  
Blanchette C(2003)Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma J Exp Med 198 851-862
[9]  
Dressman H(2003)The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma Blood 102 3871-3879
[10]  
Huang E(2002)Gene Expression Omnibus: NCBI gene expression and hybridization array data repository Nucleic Acids Res 30 207-210
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