The Ews-ERG fusion protein can initiate neoplasia from lineage-committed haematopoietic cells.
The EWS-ERG fusion protein is found in human sarcomas with the chromosomal translocation t(21;22)(q22;q12), where the translocation is considered to be an initiating event in sarcoma formation within uncommitted mesenchymal cells, probably long-lived progenitors capable of self renewal. The fusion protein may not therefore have an oncogenic capability beyond these progenitors. To assess whether EWS-ERG can be a tumour initiator in cells other than mesenchymal cells, we have analysed Ews-ERG fusion protein function in a cellular environment not typical of that found in human cancers, namely, committed lymphoid cells. We have used Ews-ERG invertor mice having an inverted ERG cDNA cassette flanked by loxP sites knocked in the Ews intron 8, crossed with mice expressing Cre recombinase under the control of the Rag1 gene to give conditional, lymphoid-specific expression of the fusion protein. Clonal T cell neoplasias arose in these mice. This conditional Ews gene fusion model of tumourigenesis shows that Ews-ERG can cause haematopoietic tumours and the precursor cells are committed cells. Thus, Ews-ERG can function in cells that do not have to be pluripotent progenitors or mesenchymal cells.
Codrington
Rosalind
R
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Pannell
Richard
R
Forster
Alan
A
Drynan
Lesley F
LF
Daser
Angelika
A
Lobato
Nati
N
Metzler
Markus
M
Rabbitts
Terence H
TH
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D019070:Cell Lineage; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D019426:Integrases / Q000378:metabolism; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013945:Thymoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism
C450460:EWS-ERG fusion protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D014157:Transcription Factors; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases