<i>TFG</i> is a novel fusion partner of <i>NOR1</i> in extraskeletal myxoid chondrosarcoma

Hisaoka, Masanori; Ishida, Toru; Imamura, Tetsuo; Hashimoto, Hiroshi

doi:10.1002/gcc.20044

Cited by 98 publications

(64 citation statements)

References 20 publications

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“…Subsequently, additional TFG fusion proteins were isolated from other malignancies, all of which involved the oligomeric amino terminus of TFG (39,40). We recently demonstrated that native TFG functions at sites of vesicle biogenesis on the ER, forming a matrix between ER exit sites and the ER-Golgi intermediate compartment, a key sorting hub for secretory cargoes in metazoan cells (32).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure

Beetz

Johnson

Schuh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of gait disorders. Their pathological hallmark is a length-dependent distal axonopathy of nerve fibers in the corticospinal tract. Involvement of other neurons can cause additional neurological symptoms, which define a diverse set of complex hereditary spastic paraplegias. We present two siblings who have the unusual combination of early-onset spastic paraplegia, optic atrophy, and neuropathy. Genome-wide SNP-typing, linkage analysis, and exome sequencing revealed a homozygous c.316C>T (p.R106C) variant in the Trk-fused gene (TFG) as the only plausible mutation. Biochemical characterization of the mutant protein demonstrated a defect in its ability to self-assemble into an oligomeric complex, which is critical for normal TFG function. In cell lines, TFG inhibition slows protein secretion from the endoplasmic reticulum (ER) and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the underlying microtubule cytoskeleton. The present study provides a unique link between altered ER architecture and neurodegeneration.membrane trafficking | COPII-mediated secretion | ER exit site H ereditary spastic paraplegias (HSPs) are a diverse group of disorders characterized by spastic weakness in the lower extremities, which results from degeneration of upper motoneuron axons in the corticospinal tract (1, 2). Based on the presence or absence of other neurological abnormalities, HSPs are classified as complicated or pure, respectively. In addition to lower-limb spasticity, complicated forms of HSP may be associated with ataxia, mental retardation, dementia, extrapyramidal signs, visual dysfunction, and/or epilepsy. HSPs are typically progressive, but age of onset is highly variable. The heterogeneity in clinical presentation is accompanied by genetic heterogeneity. To date, more than 40 different genetic loci, which include nearly all modes of inheritance, have been linked to HSPs (1-5). However, in nearly half of these cases, the identities of the causative genes remain unknown. The identification of additional HSP genes and, more importantly, the functional characterization of their encoded products, will both contribute to our understanding of the pathomechanisms underlying HSPs and reveal the general requirements for lifelong axonal maintenance.More than half the HSP cases in North America and Northern Europe can be attributed to defects in organelle dynamics (6). In particular, mutations that impact the architecture of the endoplasmic reticulum (ER) are common in patients with HSP. The ER is comprised of a network of membrane tubules and sheetlike cisternae that extend throughout the cytoplasm and encase the nucleus (7-9). Several factors contribute to this architecture, including (i) membrane-bending proteins of the REEP and reticulon families; (ii) regulators of the microtubule cytoskeleton, which governs the spatial patterning of the ER network; and (iii) components of the ear...

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Section: Resultsmentioning

confidence: 99%

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure

Beetz

Johnson

Schuh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…TFG is also the fusion partner of ALK kinase in anaplastic large cell lymphomas (13,14), and of NORI in extraskeletal myxoid chondrosarcoma (15). An attractive hypothesis is the possibility that cellular pathways involving TFG protein might be deregulated in tumors carrying TFG rearrangements.…”

Section: Discussionmentioning

confidence: 99%

“…TFG is also involved in the generation of a class of ALK oncogenes in anaplastic large cell lymphoma (13,14). Moreover, TFG has been recently detected as a novel fusion partner for NORI in extraskeletal myxoid chondrosarcoma (15). Studies performed on the normal counterpart have shown that the TFG gene is ubiquitously expressed in human adult tissues and that it is conserved among several species, including C. elegans (16).…”

Section: Shp-1 Is a Cytoplasmic Sh2 Domain Containing Protein-tyrosinmentioning

confidence: 99%

Analysis of SHP-1-mediated Down-regulation of the TRK-T3 Oncoprotein Identifies Trk-fused Gene (TFG) as a Novel SHP-1-interacting Protein

Roccato

Miranda

Raho

et al. 2005

Journal of Biological Chemistry

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“…t(9;22)(q22;q12) and t(9;17)(q22;q11) have not been found in any other tumors. t(9;15)(q22;q21), which results in the TCF12/NR4A3 fusion gene (16,27), and t(3;9)(q12;q22), which results in the TFG/NR4A3 fusion gene (28), were reported in only one case each. It is unclear whether the fusion genes identified in EMC are associated with particular morphological features and clinical significance.…”

Section: Extraskeletal Myxoid Chondrosarcoma Of the Thigh With A T(9;mentioning

confidence: 99%

Extraskeletal myxoid chondrosarcoma of the thigh with a t(9;17) translocation

et al. 2011

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Abstract. Extraskeletal myxoid chondrosarcomas (EMC) are relatively rare. We report a case of EMC of the thigh. A 41-yearold man presented with a tumor history of more than 4 months. Following open biopsy, wide resection of the tumor was performed. Histopathologically, the tumor had a multinodular architecture consisting of myxomatous areas demarcated by fibrous septa. Proliferation of uniform, round tumor cells with oval nuclei was observed. Well-formed hyaline cartilage and rhabdoid-like cells were not visible. Immunohistochemically, the tumor cells were positive for vimentin and S-100. The composite karyotype was 46,XY,t(9;17)(q22;q11),t(9;21) (q21;p13), and the diagnosis of EMC was made. No recurrence of the mass or metastasis was observed during a follow-up period of 4 years and 7 months. Only 50 cytogenetic cases of EMC, including our case, have been reported in the English literature thus far. Clinical presentation, radiological features and histopathological and cytogenetic findings are described, and the relevant literature is reviewed.

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TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma

Cited by 98 publications

References 20 publications

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure

Analysis of SHP-1-mediated Down-regulation of the TRK-T3 Oncoprotein Identifies Trk-fused Gene (TFG) as a Novel SHP-1-interacting Protein

Extraskeletal myxoid chondrosarcoma of the thigh with a t(9;17) translocation

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