title: Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy.
abstract: 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.
authors.affiliation: Institute of Pathology, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Schaefer
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Braun
authors.forename: Kristin
authors.initials: K
authors.lastname: Brachwitz
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wai
authors.forename: Uta
authors.initials: U
authors.lastname: Dirksen
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanvers-Kaminsky
authors.forename: Heribert
authors.initials: H
authors.lastname: Juergens
authors.forename: David
authors.initials: D
authors.lastname: Herrero
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegmaier
authors.forename: Ewa
authors.initials: E
authors.lastname: Koscielniak
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Michaela
authors.initials: M
authors.lastname: Nathrath
authors.forename: Georg
authors.initials: G
authors.lastname: Gosheger
authors.forename: Dominik T
authors.initials: DT
authors.lastname: Schneider
authors.forename: Carsten
authors.initials: C
authors.lastname: Bury
authors.forename: Raihanatou
authors.initials: R
authors.lastname: Diallo-Danebrock
authors.forename: Laura
authors.initials: L
authors.lastname: Ottaviano
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
mesh_terms: 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