The FET protein family (also known as the TET protein family) [1] consists of three similarly structured and functioning proteins. [2] They and the genes in the FET gene family which encode them (i.e. form the pre-messenger RNAs that are converted to the messenger RNAs responsible for their production) are: [2] [3] 1) the EWSR1 protein encoded by the EWSR1 gene (also termed the Ewing sarcoma RNA binding protein, EWS RNA binding protein 1, or bK984G1.4 gene) located at band 12.2 of the long (i.e. "q") arm of chromosome 22; [4] 2) the FUS (i.e. fused in sarcoma) protein encoded by the FUS gene (also termed the FUS RNA binding protein, TLS, asTLS, ALS6, ETM4, FUS1, POMP75, altFUS, or HNRNPP2 gene) located at band 16 on the short arm of chromosome 16; [5] and 3) the TAF15 protein encoded by the TAF15 gene (also termed the TATA-box binding protein associated factor 15, Npl3, RBP56, TAF2N, or TAFII68 gene) located at band 12 on the long arm of chromosome 7 [6] The FET in this protein family's name derives from the first letters of FUS, EWSR1, and TAF15. [7]
FET proteins are abundantly expressed in virtually all tissues examined. They are RNA-binding proteins. [7] By binding to their RNA targets, they contribute to the regulation of: a) the transcription of genes into pre-messenger RNA, the splicing of pre-messenger RNA into mature messenger RNA, and the transport of these RNAs between different areas of their parent cells; b) the processing of micro-RNAs that are involved in RNA silencing and post-transcriptional regulation of gene expression; and c) the detection and repair of damaged DNA. Through these multiple, complex, and often incompletely understood actions, the FET family proteins regulate the cellular expression of diverse genes. [2] However, the genes for FET proteins often undergo various types of mutation. While these mutations and the diseases with which they are associated can be found in the Wikipedia pages on these diseases, this article focuses on one type of mutation, the fusion gene mutation. Fusion genes are formed from two previously independent genes that become united due to a chromosome translocation, deletion of some genetic material in a chromosome, or chromosomal inversion. [1] [8] For example, the EWSR1-FL1 [9] fusion gene is made by a chromosomal translocation which merges part of the EWSR1 gene normally located on band 12 of the long (or "q") arm of chromosome 22 with part of the FLI1 ETS transcription factor family gene normally located on band 24 of the long arm of chromosome 11. The EWSR1-FLI1 fusion gene encodes an EWS-FLI1 chimeric protein which possesses unregulated and excessive FLI1 transcription factor activity which it appears to contribute to the development of Ewing sarcomas. [10] FET fusion genes have attracted recent interest because they have been found to be associated with, and may act to promote the development of, a wide range of soft tissue neoplasms derived from mesencyhmal tissue cells. [3] [7] [11] Detection of a FET gene–containing fusion gene is extremely helpful in diagnosing tumor types, [1] [11] defining the pathogenic mechanisms by which these fusion proteins promote disorders, [3] [12] and thereby identifying potential targets for treating these disorders. [2] [13] The following are examples of these fusion genes' associations with malignant and benign neoplastic tumors. [1] [7]