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Virchows Archiv
Published in: Virchows Archiv 6/2014

01-12-2014 | Original Article

Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis

Authors: M. Lieveld, E. Bodson, G. De Boeck, B. Nouman, A. M. Cleton-Jansen, E. Korsching, M. S. Benassi, P. Picci, G. Sys, B. Poffyn, N. A. Athanasou, P. C. W. Hogendoorn, R. G. Forsyth

Published in: Virchows Archiv | Issue 6/2014

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Abstract

Giant cell tumor of bone (GCTB) displays worrisome clinical features such as local recurrence and occasionally metastatic disease which are unpredictable by morphology. Additional routinely usable biomarkers do not exist. Gene expression profiles of six clinically defined groups of GCTB and one group of aneurysmal bone cyst (ABC) were determined by microarray (n = 33). The most promising differentially expressed genes were validated by Q-PCR as potential biomarkers in a larger patient group (n = 41). Corresponding protein expression was confirmed by immunohistochemistry. Unsupervised hierarchical clustering reveals a metastatic GCTB cluster, a heterogeneous, non-metastatic GCTB cluster, and a primary ABC cluster. Balanced score testing indicates that lumican (LUM) and decorin (DCN) are the most promising biomarkers as they have lower level of expression in the metastatic group. Expression of dermatopontin (DPT) was significantly lower in recurrent tumors. Validation of the results was performed by paired and unpaired t test in primary GCTB and corresponding metastases, which proved that the differential expression of LUM and DCN is tumor specific rather than location specific. Our findings show that several genes related to extracellular matrix integrity (LUM, DCN, and DPT) are differentially expressed and may serve as biomarkers for metastatic and recurrent GCTB.
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Metadata
Title
Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis
Authors
M. Lieveld
E. Bodson
G. De Boeck
B. Nouman
A. M. Cleton-Jansen
E. Korsching
M. S. Benassi
P. Picci
G. Sys
B. Poffyn
N. A. Athanasou
P. C. W. Hogendoorn
R. G. Forsyth
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 6/2014
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-014-1666-7

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