ETV6 gene aberrations in non-haematological malignancies: A review highlighting ETV6 associated fusion genes in solid tumors

Abstract

ETV6 (translocation-Ets-leukemia virus) gene is a transcriptional repressor mainly involved in haematopoiesis and maintenance of vascular networks and has developed to be a major oncogene with the potential ability of forming fusion partners with many other genes with carcinogenic consequences. ETV6 fusions function primarily by constitutive activation of kinase activity of the fusion partners, modifications in the normal functions of ETV6 transcription factor, loss of function of ETV6 or the partner gene and activation of a proto-oncogene near the site of translocation. The role of ETV6 fusion gene in tumorigenesis has been well-documented and more variedly found in haematological malignancies. However, the role of the ETV6 oncogene in solid tumors has also risen to prominence due to an increasing number of cases being reported with this malignancy. Since, solid tumors can be well-targeted, the diagnosis of this genre of tumors based on ETV6 malignancy is of crucial importance for treatment. This review highlights the important ETV6 associated fusions in solid tumors along with critical insights as to existing and novel means of targeting it. A consolidation of novel therapies such as immune, gene, RNAi, stem cell therapy and protein degradation hitherto unused in the case of ETV6 solid tumor malignancies may open further therapeutic avenues.