Genetics and Epigenetics of the TET-ETS Translocation Network

Abstract

Abstract:In the present paper we review the translocation network involving TET and ETS family members with special focus on the Ewing family of tumors. FUS (fusion, involved in t(12;16) in malignant liposarcoma = TLS, Translocated in liposarcoma), EWSR1 (Ewing sarcoma breakpoint region 1) and TAF15 (TATA box-binding protein-associated factor, 68-KD) are the three human members of the TET family of RNA binding proteins. In addition, two EWSR1 pseudogenes are present in the human genome. TET family members are involved in several oncogenic gene fusions. Five of the 18 known fusion partners belong to the E26 (E twenty-six, ETS) family of transcription factors. Gene fusions between TET or ETS family members and other fusion partners link these gene fusions to a large network of oncogenic gene rearrangements.

Characterization of Ewing sarcoma associated cancer/testis antigens

“…Several different gene fusions between TET family members and a plethora of fusion partners have been described (for a review, see ref. 1). Patients with localized EFT treated with a conventional multimodal therapy regime have a 5-year-survival of approximately 65%, whereas patients with primary metastases have only a five-year-survival of 25%.…”

“…The chimeric aberrant transcription factors of the TET-ETS family play a central role in malignant transformation and proliferation of EFT. 1 Unfortunately, the fusion region of the most common EWSR1-Friend leukemia virus integration 1 (FLI1) onco-fusion proteins encode only weak HLA class I binding peptides for common HLA molecules. 9 However, down-stream targets of TET-ETS in combination with a CTAexpression profile are interesting targets for immunotherapy.…”

Lipases and Related Molecules in Cancer

“…Interestingly, gene fusions between ACSL3 and the transcription factor ETV1 (v-ets erythroblastosis virus E26 oncogene homolog E-26 variant 1) have been found in prostate cancer. 93 In contrast to many other gene fusions involving members of the ETS (E twenty six) family of transcription factors, 32 these gene fusions did not result in the expression of fusion proteins but lead to expression of truncated ETV1 proteins as a consequence of high activity of the ACSL3 promotor in the prostate. LIPE is also involved in cancer cachexia.…”

“…32 These fusion proteins act as aberrant transcription factors and are involved in the pathogenesis of ET. Therefore, molecular targeting of fusion proteins might be an interesting strategy for molecular therapy of ET.…”

A short treatise concerning a musical approach for the interpretation of gene expression data

“…At the molecular level, neuroblastoma cells and Ewing sarcoma cells show several specific alterations. For example, Ewing sarcomas express tumour-specific TET-ETS fusion transcripts 3 . In addition, the gene expression profile of these tumours is highly different and microarray analysis can be used for identification of Ewing sarcoma samples 2 4 .…”