Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy.
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.
Schaefer
Karl-Ludwig
KL
Institute of Pathology, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf, Germany.
Eisenacher
Martin
M
Braun
Yvonne
Y
Brachwitz
Kristin
K
Wai
Daniel H
DH
Dirksen
Uta
U
Lanvers-Kaminsky
Claudia
C
Juergens
Heribert
H
Herrero
David
D
Stegmaier
Sabine
S
Koscielniak
Ewa
E
Eggert
Angelika
A
Nathrath
Michaela
M
Gosheger
Georg
G
Schneider
Dominik T
DT
Bury
Carsten
C
Diallo-Danebrock
Raihanatou
R
Ottaviano
Laura
L
Gabbert
Helmut E
HE
Poremba
Christopher
C
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D016158:Genes, p53; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D020125:Mutation, Missense / Q000235:genetics; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary