Genomes and Genes
rna binding protein fus
Summary: A multifunctional heterogeneous-nuclear ribonucleoprotein that may play a role in homologous DNA pairing and recombination. The N-terminal portion of protein is a potent transcriptional activator, while the C terminus is required for RNA binding. The name FUS refers to the fact that genetic recombination events result in fusion oncogene proteins (ONCOGENE PROTEINS, FUSION) that contain the N-terminal region of this protein. These fusion proteins have been found in myxoid liposarcoma (LIPOSARCOMA, MYXOID) and acute myeloid leukemia.
- Fujii R, Takumi T. TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines. J Cell Sci. 2005;118:5755-65 pubmed..Our results demonstrate that TLS associates with mRNA encoding an actin-related protein and may be involved in actin reorganization in spines. ..
- Perrotti D, Bonatti S, Trotta R, Martinez R, Skorski T, Salomoni P, et al. TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis. EMBO J. 1998;17:4442-55 pubmed..Together, these results suggest that FUS might function as a regulator of BCR/ABL leukemogenesis, promoting growth factor independence and preventing differentiation via modulation of cytokine receptor expression. ..
- Vance C, Rogelj B, HortobÃ¡gyi T, De Vos K, Nishimura A, Sreedharan J, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323:1208-1211 pubmed publisher..FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration. ..
- Shing D, McMullan D, Roberts P, Smith K, Chin S, Nicholson J, et al. FUS/ERG gene fusions in Ewing's tumors. Cancer Res. 2003;63:4568-76 pubmed..Our data provide additional evidence that the transactivation domains of the TET family of RNA-binding proteins (such as EWS and FUS) are interchangeable, and suggests a novel mechanism of oncogenesis in Ewing's tumors. ..
- Law W, Cann K, Hicks G. TLS, EWS and TAF15: a model for transcriptional integration of gene expression. Brief Funct Genomic Proteomic. 2006;5:8-14 pubmed
- Stolow D, Haynes S. Cabeza, a Drosophila gene encoding a novel RNA binding protein, shares homology with EWS and TLS, two genes involved in human sarcoma formation. Nucleic Acids Res. 1995;23:835-43 pubmed..Therefore, it appears that these genes constitute a new sub-family of RNA binding proteins. ..
- Seelaar H, Klijnsma K, de Koning I, van der Lugt A, Chiu W, Azmani A, et al. Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration. J Neurol. 2010;257:747-53 pubmed publisher..The existence of this pathological subtype can be predicted with reasonable certainty by age at onset <or=40 years, negative family history, bvFTD and caudate atrophy on MRI. ..
- Rapp T, Yang L, Conrad E, Mandahl N, Chansky H. RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells. J Orthop Res. 2002;20:723-9 pubmed..When considered in conjunction with studies on other sarcoma fusion proteins, these data suggest that aberrant RNA splicing may be a common feature of human sarcomas...
- Melot T, Dauphinot L, Sevenet N, Radvanyi F, Delattre O. Characterization of a new brain-specific isoform of the EWS oncoprotein. Eur J Biochem. 2001;268:3483-9 pubmed..The phylogenetic conservation and relationship to neural differentiation strongly suggests an important functional role for this exon. ..
- Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar H, Mackenzie I. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain. 2009;132:2922-31 pubmed publisher..These findings suggest that FUS is the pathological protein in a significant subgroup of sporadic FTD and reinforce the concept that FTD and amyotrophic lateral sclerosis are closely related conditions. ..
- Zinszner H, Immanuel D, Yin Y, Liang F, Ron D. A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibited. Oncogene. 1997;14:451-61 pubmed
- Guipaud O, Guillonneau F, Labas V, Praseuth D, Rossier J, Lopez B, et al. An in vitro enzymatic assay coupled to proteomics analysis reveals a new DNA processing activity for Ewing sarcoma and TAF(II)68 proteins. Proteomics. 2006;6:5962-72 pubmed..This common activity suggests a role for TET proteins and PSF in genome plasticity control. ..
- Belly A, Moreau Gachelin F, Sadoul R, Goldberg Y. Delocalization of the multifunctional RNA splicing factor TLS/FUS in hippocampal neurones: exclusion from the nucleus and accumulation in dendritic granules and spine heads. Neurosci Lett. 2005;379:152-7 pubmed..The apparent removal of TLS from the nucleus might result in specific patterns of mRNA transcription or splicing in hippocampal neurones. TLS may also contribute to steering, anchoring or regulating mRNAs at synaptic sites. ..
- Lagier Tourenne C, Cleveland D. Rethinking ALS: the FUS about TDP-43. Cell. 2009;136:1001-4 pubmed publisher..TDP-43 and FUS/TLS have striking structural and functional similarities, implicating alterations in RNA processing as a key event in ALS pathogenesis. ..
- Goransson M, Andersson M, Forni C, Stahlberg A, Andersson C, Olofsson A, et al. The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-kappaB target genes by interaction with NFKBIZ. Oncogene. 2009;28:270-8 pubmed publisher..Similar mechanisms may be a part of the transformation process in other tumor types carrying FUS, EWSR1 and TAF15 containing fusion oncogenes...
- Yoshimura A, Fujii R, Watanabe Y, Okabe S, Fukui K, Takumi T. Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines. Curr Biol. 2006;16:2345-51 pubmed..Our results demonstrate that myosin-Va facilitates the transport of TLS-containing mRNP complexes in spines and may function in synaptic plasticity through Ca2+ signaling. ..
- Olofsson A, Willen H, Göransson M, Engström K, Meis Kindblom J, Stenman G, et al. Abnormal expression of cell cycle regulators in FUS-CHOP carrying liposarcomas. Int J Oncol. 2004;25:1349-55 pubmed..We conclude that deregulation of G1 controlling proteins is common in MLS/RCLS and that aberrant expression of these proteins is of importance in the pathogenesis of this tumor type...
- Neumann M, Roeber S, Kretzschmar H, Rademakers R, Baker M, Mackenzie I. Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol. 2009;118:605-16 pubmed publisher..No mutation in the FUS gene was identified in a single case with DNA available. These findings suggest that FUS may play an important role in the pathogenesis of NIFID. ..
- Engström K, Willen H, Kåbjörn Gustafsson C, Andersson C, Olsson M, Göransson M, et al. The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells. Am J Pathol. 2006;168:1642-53 pubmed..In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene...
- Kwiatkowski T, Bosco D, Leclerc A, Tamrazian E, Vanderburg C, Russ C, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009;323:1205-8 pubmed publisher..Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders. ..
- Bertrand P, Akhmedov A, Delacote F, Durrbach A, Lopez B. Human POMp75 is identified as the pro-oncoprotein TLS/FUS: both POMp75 and POMp100 DNA homologous pairing activities are associated to cell proliferation. Oncogene. 1999;18:4515-21 pubmed..Possible relationship between cell proliferation, response to DNA damage and DNA homologous pairing activity of the pro-oncoprotein TLS/FUS are discussed. ..
- Morohoshi F, Ootsuka Y, Arai K, Ichikawa H, Mitani S, Munakata N, et al. Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes. Gene. 1998;221:191-8 pubmed
- Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H, et al. Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. Genomics. 1996;37:1-8 pubmed..These observations indicate that FUS and EWS belong to the housekeeping type of genes. This view is supported by the presence of the housekeeping gene type of promoter region in both genes. ..
- Kuroda M, Sok J, Webb L, Baechtold H, Urano F, Yin Y, et al. Male sterility and enhanced radiation sensitivity in TLS(-/-) mice. EMBO J. 2000;19:453-62 pubmed..These results are consistent with a role for TLS in homologous DNA pairing and recombination. ..
- Bertolotti A, Lutz Y, Heard D, Chambon P, Tora L. hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. EMBO J. 1996;15:5022-31 pubmed..Moreover, we demonstrate that hTAF(II)68 co-purifies also with the human RNA polymerase II and can enter the preinitiation complex together with Pol II. ..
- Rabbitts T, Forster A, Larson R, Nathan P. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet. 1993;4:175-80 pubmed..The data also indicate the importance of transcription disruption in the pathogenesis of solid tumours. ..
- Sato S, Idogawa M, Honda K, Fujii G, Kawashima H, Takekuma K, et al. Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing. Gastroenterology. 2005;129:1225-36 pubmed..Certain mRNA splicing abbreviations seen in human cancers may be induced by the activation of the Wnt signaling pathway. ..
- Riggi N, Cironi L, Provero P, Suva M, Stehle J, Baumer K, et al. Expression of the FUS-CHOP fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma. Cancer Res. 2006;66:7016-23 pubmed..Taken together, our observations suggest that expression of FUS-CHOP may be the initiating event in myxoid liposarcoma pathogenesis, and that MPCs may constitute one cell type from which these tumors originate...
- Panagopoulos I, Hoglund M, Mertens F, Mandahl N, Mitelman F, Aman P. Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene. 1996;12:489-94 pubmed
- Zinszner H, Sok J, Immanuel D, Yin Y, Ron D. TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling. J Cell Sci. 1997;110 ( Pt 15):1741-50 pubmed..These findings are discussed in the context of the role altered forms of TLS play in cellular transformation. ..
- Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993;363:640-4 pubmed..In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation. ..
- Walsby E, Gilkes A, Tonks A, Darley R, Mills K. FUS expression alters the differentiation response to all-trans retinoic acid in NB4 and NB4R2 cells. Br J Haematol. 2007;139:94-7 pubmed
- Andersson M, Ståhlberg A, Arvidsson Y, Olofsson A, Semb H, Stenman G, et al. The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol. 2008;9:37 pubmed publisher..Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer. ..
- Thelin Järnum S, Göransson M, Burguete A, Olofsson A, Aman P. The myxoid liposarcoma specific TLS-CHOP fusion protein localizes to nuclear structures distinct from PML nuclear bodies. Int J Cancer. 2002;97:446-50 pubmed..Transfection of TLS-CHOP induced a rapid disappearance of PCNA. TLS-CHOP may disturb the nuclear machinery by binding and sequestering important factors from their natural sites...
- Kasyapa C, Kunapuli P, Cowell J. Mass spectroscopy identifies the splicing-associated proteins, PSF, hnRNP H3, hnRNP A2/B1, and TLS/FUS as interacting partners of the ZNF198 protein associated with rearrangement in myeloproliferative disease. Exp Cell Res. 2005;309:78-85 pubmed..In 293 cells expressing the ZNF198/FGFR1 fusion protein, neither PSF nor PTB binds to the fusion protein, possibly because of their differential localization in the cell. ..
- van Blitterswijk M, Landers J. RNA processing pathways in amyotrophic lateral sclerosis. Neurogenetics. 2010;11:275-90 pubmed publisher..In this review, we will discuss six ALS-related, RNA processing genes including their discovery, function, and commonalities. ..
- Pimentel H, Parra M, Gee S, Mohandas N, Pachter L, Conboy J. A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis. Nucleic Acids Res. 2016;44:838-51 pubmed publisher..High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with ..
- Lagier Tourenne C, Polymenidou M, Cleveland D. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet. 2010;19:R46-64 pubmed publisher..Their association with ALS and other neurodegenerative diseases is redirecting research efforts toward understanding the role of RNA processing regulation in neurodegeneration. ..
- Suster S, Morrison C. Sclerosing poorly differentiated liposarcoma: clinicopathological, immunohistochemical and molecular analysis of a distinct morphological subtype of lipomatous tumour of soft tissue. Histopathology. 2008;52:283-93 pubmed publisher..The tumours described appear to represent an unusual morphological variant of poorly differentiated liposarcoma associated with aggressive behaviour, and may represent a common end-stage pathway for various types of liposarcoma. ..
- ChiÃ² A, Restagno G, Brunetti M, Ossola I, Calvo A, Mora G, et al. Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation. Neurobiol Aging. 2009;30:1272-5 pubmed publisher..R514S mutation and bulbar onset, with very young age and a rapid course in the family carrying the p.P525L mutation. ..
- Yang S, Warraich S, Nicholson G, Blair I. Fused in sarcoma/translocated in liposarcoma: a multifunctional DNA/RNA binding protein. Int J Biochem Cell Biol. 2010;42:1408-11 pubmed publisher..The FUS/TLS mutations identified in ALS patients suggests that altered RNA metabolism may play a role in ALS pathogenesis. ..
- Selamat W, Jamari I, Wang Y, Takumi T, Wong F, Fujii R. TLS interaction with NMDA R1 splice variant in retinal ganglion cell line RGC-5. Neurosci Lett. 2009;450:163-6 pubmed publisher..These results suggested that TLS might be involved in a calcium-dependent trafficking of specific NR1 splice variants in RGCs. ..
- Swetha R, Ramaiah S, Anbarasu A. R521C and R521H mutations in FUS result in weak binding with KaryopherinÎ²2 leading to Amyotrophic lateral sclerosis: a molecular docking and dynamics study. J Biomol Struct Dyn. 2017;35:2169-2185 pubmed publisherFused in sarcoma (FUS) gene encodes the RNA binding protein FUS. This gene is mapped to chromosome 16p11.2...
- Raddaoui E, Donner L, Panagopoulos I. Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous histiocytoma. Diagn Mol Pathol. 2002;11:157-62 pubmed..Because identical fusion of the and genes has been recently reported in another case of angiomatoid fibrous histiocytoma, fusion of these genes may be characteristic for at least a subset of these tumors. ..
- Immanuel D, Zinszner H, Ron D. Association of SARFH (sarcoma-associated RNA-binding fly homolog) with regions of chromatin transcribed by RNA polymerase II. Mol Cell Biol. 1995;15:4562-71 pubmed..We conclude that SARFH and, by homology, EWS and TLS participate in a function common to the expression of most genes transcribed by RNA Pol II. ..
- Kuroda M, Wang X, Sok J, Yin Y, Chung P, Giannotti J, et al. Induction of a secreted protein by the myxoid liposarcoma oncogene. Proc Natl Acad Sci U S A. 1999;96:5025-30 pubmed..TLS-CHOP thus leads to the unscheduled expression of a gene that is normally associated with adipocytic differentiation...
- Wakabayashi Ito N, Belvin M, Bluestein D, Anderson K. fusilli, an essential gene with a maternal role in Drosophila embryonic dorsal-ventral patterning. Dev Biol. 2001;229:44-54 pubmed
- Valdmanis P, Daoud H, Dion P, Rouleau G. Recent advances in the genetics of amyotrophic lateral sclerosis. Curr Neurol Neurosci Rep. 2009;9:198-205 pubmed..The findings help to better delineate the types of genes and genetic variants that are involved in ALS and provide substantial material for future research. ..
- Downs Kelly E, Goldblum J, Patel R, Weiss S, Folpe A, Mertens F, et al. The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms. Am J Surg Pathol. 2008;32:8-13 pubmed..FISH is capable of providing specific ancillary information useful in this often difficult differential diagnosis. ..
- Hallier M, Lerga A, Barnache S, Tavitian A, Moreau Gachelin F. The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS. J Biol Chem. 1998;273:4838-42 pubmed..This effect is counterpoised in vivo by Spi-1. These data suggest that alteration of pre-mRNA alternative splicing by Spi-1 could be involved in the transformation of an erythroblastic cell. ..
- Baumer D, Hilton D, Paine S, Turner M, Lowe J, Talbot K, et al. Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations. Neurology. 2010;75:611-8 pubmed publisher..The FUS c.1574C>T (P525L) and c.1554_1557delACAG mutations are associated with this distinct phenotype. The molecular genetic relationship with frontotemporal lobar degeneration with FUS pathology remains to be clarified. ..
- Yan J, Deng H, Siddique N, Fecto F, Chen W, Yang Y, et al. Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia. Neurology. 2010;75:807-14 pubmed publisher..79% in all FALS. The pathogenicity of some of these novel mutations awaits further studies. Patients with FUS mutations manifest earlier symptom onset, a higher rate of bulbar onset, and shorter duration of symptoms. ..
- Yamamoto Watanabe Y, Watanabe M, Okamoto K, Fujita Y, Jackson M, Ikeda M, et al. A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: a clinical, pathological and genetic report. J Neurol Sci. 2010;296:59-63 pubmed publisher..While atrophy and weakness of the sternocleidomastoideus muscle is not emphasized in previous reports, this symptom may be a clinical hallmark of ALS6. ..
- Silverman J, Hamilton J, Tamsen A. Benign recurring lipoblastoma in an adult versus well differentiated subcutaneous myxoid liposarcoma: clinicopathologic, immunohistochemical and molecular analysis of a unique case. Pathol Res Pract. 1999;195:787-92; discussion 793 pubmed..Based on this review and on the growth pattern, anatomic features and molecular data from the present case, we conclude that this tumor may represent the first reported case of adult LB. ..
- Groen E, van Es M, Van Vught P, Spliet W, van Engelen Lee J, de Visser M, et al. FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands. Arch Neurol. 2010;67:224-30 pubmed publisher..Although the phenotype associated with FUS mutations is variable, most patients predominantly demonstrate loss of lower motor neurons and have short disease survival. ..
- Göransson M, Wedin M, Aman P. Temperature-dependent localization of TLS-CHOP to splicing factor compartments. Exp Cell Res. 2002;278:125-32 pubmed..Further, mutational analysis of the N-terminal part of green fluorescent protein-tagged TLS-CHOP identifies a region within the N-terminal required for colocalization with the splicing factor SC-35. ..
- Takumi T. [Biological anomalies of mental diseases are located in spines?]. Tanpakushitsu Kakusan Koso. 2006;51:2328-33 pubmed
- Suzuki N, Aoki M, Warita H, Kato M, Mizuno H, Shimakura N, et al. FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion. J Hum Genet. 2010;55:252-4 pubmed publisher..Degeneration in multiple systems and cytoplasmic basophilic inclusion bodies were found in the autopsied cases. ..
- Van Langenhove T, Van der Zee J, Sleegers K, Engelborghs S, Vandenberghe R, Gijselinck I, et al. Genetic contribution of FUS to frontotemporal lobar degeneration. Neurology. 2010;74:366-71 pubmed publisher..At this point, the biologic relevance of this mutation remains elusive. Screening of additional FTLD patient cohorts will be needed to further elucidate the contribution of FUS mutations to FTLD pathogenesis. ..
- Willeke F, Ridder R, Mechtersheimer G, Schwarzbach M, Duwe A, Weitz J, et al. Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications. Clin Cancer Res. 1998;4:1779-84 pubmed..Furthermore, using FUS-CHOP fusion transcripts as targets in reverse transcription-PCR assays, we detected disseminated tumor cells in peripheral blood or bone marrow in 3 of 5 patients undergoing surgery for soft tissue liposarcoma. ..
- Millecamps S, Salachas F, Cazeneuve C, Gordon P, Bricka B, Camuzat A, et al. SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype-phenotype correlations. J Med Genet. 2010;47:554-60 pubmed publisher..This study identifies new genetic associations with ALS and provides phenotype-genotype correlations with both previously reported and novel mutations. ..
- Meissner M, Lopato S, Gotzmann J, Sauermann G, Barta A. Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins. Exp Cell Res. 2003;283:184-95 pubmed..Coimmunolocalization confirmed the nuclear matrix association and interaction of TLS/FUS with PTB, SR proteins, and SRm160. Our results suggest that the matrix protein TLS/FUS plays a role in spliceosome assembly. ..
- Higuchi M, Suzuki H, Shio Y, Hoshi S, Gotoh M. Successfully resected intrathoracic low-grade fibromyxoid sarcoma. Gen Thorac Cardiovasc Surg. 2010;58:348-51 pubmed publisher..Tumor resection was performed with a free surgical margin, and the resultant chest wall defect was repaired using prosthetic mesh. The patient has been well without any recurrence for 18 months since surgery. ..
- Perani M, Antonson P, Hamoudi R, Ingram C, Cooper C, Garrett M, et al. The proto-oncoprotein SYT interacts with SYT-interacting protein/co-activator activator (SIP/CoAA), a human nuclear receptor co-activator with similarity to EWS and TLS/FUS family of proteins. J Biol Chem. 2005;280:42863-76 pubmed..This region encompasses the SNF11 binding domain (amino acids 156-211), which interacts specifically with SYT in vivo and in vitro. ..
- Panagopoulos I, Möller E, Dahlén A, Isaksson M, Mandahl N, Vlamis Gardikas A, et al. Characterization of the native CREB3L2 transcription factor and the FUS/CREB3L2 chimera. Genes Chromosomes Cancer. 2007;46:181-91 pubmed..Thus, studies regarding the pathways influenced by wild-type CREB3L2 should provide valuable clues to the pathogenetic significance of the FUS/CREB3L2 chimera in low grade fibromyxoid sarcoma. ..