The EWS protein is dispensable for Ewing tumor growth.
EWS encodes a ubiquitously expressed RNA binding protein with largely unknown function. In Ewing sarcoma family tumors (EFT), one allele is rearranged with an ETS gene. This is the first description of an EFT with a complete EWS deficiency in the presence of two copies of a rearranged chromosome 22 carrying an interstitial EWS-FLI1 translocation. Absence of EWS protein suggested that it is dispensable for EFT growth. By sequencing of EWS cDNA from unrelated EFTs, we excluded inactivation of EWS as a general mechanism in EFT pathogenesis. Rather, EWS was found to be uniformly expressed in two splicing variants of similar abundancy, EWSalpha and EWSbeta, which differ in a single amino acid. Three EWS negative cell lines were established, which will serve as valuable models to study normal and aberrant EWS function upon reintroduction into the tumor cells.
Kovar
H
H
Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090 Vienna, Austria. kovar@ccri.univie.ac.at
Jug
G
G
Hattinger
C
C
Spahn
L
L
Aryee
D N
DN
Ambros
P F
PF
Zoubek
A
A
Gadner
H
H
D000483:Alleles; D017398:Alternative Splicing; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D020868:Gene Silencing; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins / Q000235:genetics* / Q000502:physiology; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
C106031:EWS-FLI fusion protein; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins; D014157:Transcription Factors