TY - JOUR
T1 - Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy
AU - Schaefer, Karl Ludwig
AU - Eisenacher, Martin
AU - Braun, Yvonne
AU - Brachwitz, Kristin
AU - Wai, Daniel H.
AU - Dirksen, Uta
AU - Lanvers-Kaminsky, Claudia
AU - Juergens, Heribert
AU - Herrero, David
AU - Stegmaier, Sabine
AU - Koscielniak, Ewa
AU - Eggert, Angelika
AU - Nathrath, Michaela
AU - Gosheger, Georg
AU - Schneider, Dominik T.
AU - Bury, Carsten
AU - Diallo-Danebrock, Raihanatou
AU - Ottaviano, Laura
AU - Gabbert, Helmut E.
AU - Poremba, Christopher
N1 - Funding Information:
This work was supported by grants from the ‘Forschungskommission der Medizinischen Fakultaet Duesseldorf’, and the ‘Madeleine Schickedanz-KinderKrebs-Stiftung’.
PY - 2008/3
Y1 - 2008/3
N2 - In Ewing's sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy. To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH, and WNT1-signalling. Regression of primary tumours (n = 20) induced by polychemotherapy was found to be correlated with the expression of genes involved in angiogenesis, apoptosis, ubiquitin proteasome pathway, and PI3 kinase and p53 pathways. These findings could be confirmed by in vitro cytotoxicity assays. A set of 46 marker genes correctly classifies these 20 tumours as responding versus non-responding. We conclude that expression signatures of initial tumour biopsies can help to identify ESFT patients at high risk to develop tumour metastasis or to suffer from a therapy refractory cancer.
AB - In Ewing's sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy. To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH, and WNT1-signalling. Regression of primary tumours (n = 20) induced by polychemotherapy was found to be correlated with the expression of genes involved in angiogenesis, apoptosis, ubiquitin proteasome pathway, and PI3 kinase and p53 pathways. These findings could be confirmed by in vitro cytotoxicity assays. A set of 46 marker genes correctly classifies these 20 tumours as responding versus non-responding. We conclude that expression signatures of initial tumour biopsies can help to identify ESFT patients at high risk to develop tumour metastasis or to suffer from a therapy refractory cancer.
KW - Ewing's sarcoma family of tumours
KW - Expression analysis
KW - Oligonucleotide microarray
KW - Prognosis
KW - Response to chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=40849114332&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2008.01.020
DO - 10.1016/j.ejca.2008.01.020
M3 - Article
C2 - 18294840
AN - SCOPUS:40849114332
SN - 0959-8049
VL - 44
SP - 699
EP - 709
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 5
ER -
