Even our data showed that NONOTF RCC patients had a longer survival than ASPSCR1TF RCC and PRCCTF RCC in a short time followup study However, there was a case at the pT1aM0N0 stage Significance By conditionally expressing in mice the fusion gene ASPSCR1TF from human alveolar soft part sarcoma (ASPS), we generated a model that recapitulates the human tumor histologically and by expression profile, enabling study of the conditions supportive of tumor development Mouse tumors demonstrated angiogenic gene expression in the frank absence ofASPSCR1TF fusion protein may interfere with or obviate the normal activation or dimerization functions of TEF3 to the extent that normal transcription is deranged TEF3 may bind an alternative transcription factor, leading to aberrant transcriptional programs or simply homodimerize in the
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Aspscr1-tfe3- Cases with ASPSCR1TF, SFPQTF, PRCCTF, and NONOTF gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant ofAspscr1 Tfe3 Fusion Translocation Fish Probe Kit 10 Tests Diagnostic Technology 2 Aspscr1 Gene Genecards Aspc1 Protein Aspc1 Antibody Kidney Renal Cell Carcinoma With T X 17 P11 Q25 Aspscr1 Tfe3 Aspscr1 Recombinant Protein Anti Aspscr1 Antibody Rabbit
Molecular Landscape In Alveolar Soft Part Sarcoma Implications For Molecular Targeted Therapy Sciencedirect
The ASPSCR1TF gene fusion is the same gene fusion found in alveolar soft part sarcoma (ASPS), a rare pediatric neoplasm of uncertain histogenesis However, the translocation in Xp11 translocation RCC is balanced, which may contribute to the differences seen at the clinical and histopathologic levels between Xp11 translocation RCC and ASPSAlveolar soft part sarcoma (ASPS) is an exceptionally rare nonrhabdomyosarcomatous soft tissue sarcoma (NRSTS), characterized by the translocation t(X;17) p(112;q25) This translocation results i ASPSCR1TF fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes Apart from tumors with MED15TF fusion
Another tumor, a rare subset of papillary renal cell carcinoma (RCC) with a distinctive pathologic morphology, has rearrangements of TF with ASPSCR1 or other fusion partner genes This tumor predominantly affects children and young adults, presents at an advanced stage but with an indolent clinical course, and is a distinct entity in theWhen a TF rearrangement is identified, reflex testing using the TF/ASPSCR1 probe will be performed Method Name A short description of the method used to perform the test Fluorescence In Situ Hybridization (FISH)Translocation t(X;17)(p11;q25) of this gene with transcription factor TF gene results in a ASPSCR1TF fusion protein in alveolar soft part sarcoma and in renal cell carcinomas Multiple alternatively spliced transcript variants have been found provided by RefSeq, Oct 11 Gencode Transcript ENST Gencode Gene
Oncogenic rearrangements of the TF transcription factor gene are found in two distinct human cancers These include ASPSCR1TF in all cases of alveolar soft part sarcoma (ASPS) and ASPSCR1TF, PRCCTF, SFPQTF and others in a subset of paediatric and adult RCCs Here we examined the functiIn genetic analysis, ASPSCR1TF fusion was detected by RTPCR and direct sequence In conjunction with the histological and immunohistochemical findings as well as genetic analysis, the mass was diagnosed as an orbital ASPS Download Download highres image (3MB) Download Download fullsize image; Amy Ruffle, Malcolm Cameron, Nicolaas Jonas, Samantha Levine, Caroline Mills, C Elizabeth Hook, Matthew J Murray, Lingual Alveolar Soft Part Sarcoma in a 1YearOld Infant Youngest Reported Case With Characteristic ASPSCR1TF Fusion, Pediatric and Developmental Pathology, /, (), (19)
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Alveolar Soft Part Sarcomas Molecular Pathogenesis And Implications For Novel Targeted Therapies
Aims Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumour with unique morphology and a recurrent, nonreciprocal translocation der(17)t(X;17)(p112;q25) leading to the fusion of ASPSCR1 (also known as ASPL) to the transcription factor TF Although diagnosis is straightforward in classical cases, tumours with atypical morphological features may be difficult to classify solely onOur results demonstrate that the most sensitive marker of alveolar soft part sarcoma was the presence of the ASPSCR1TF fusion transcript Thus, detection of the ASPSCR1TF fusion transcript was considered applicable for formalinfixed, paraffinembedded tissues with superior sensitivity as compared with TF immunohistochemical stainingContext PubMed ASPSCR1 Title/Abstract AND TF Title/Abstract AND fusion Title/Abstract Functional or gene categories assigned by FusionGDB annotation Oncogene involved fusion gene, inframe and retained their domain * DoF score (Degree of Frequency) = # partners X # break points X # cancer types
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Three cases demonstrated known fusions ASPSCR1TF, MED15TF, and RBM10TF However, case 1 showed a NEAT1TF fusion gene due to a t(X;11)(p1123; Alveolar soft part sarcoma (ASPS) is a rare malignancy that, since its initial description, remains a neoplasm of uncertain histogenesis The diseasedefining molecular event characterizing the diagnosis of ASPS is the ASPSCR1TF fusion gene Following identification of an index case of ASPS withTF is also rearranged with ASPSCR1 and other genes in rare forms of renal cell carcinoma, which are most common in children 42 Interestingly, the TFASPSCR1 translocations in the renal cell carcinomas tend to be balanced, whereas the translocation is unbalanced in alveolar soft part sarcoma (Fig 1812A)
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In this instance, the ASPSCR1TF gene product functions as a lactate transporter Strikingly, every mouse in which the gene was up regulated developed a tumor The locations of tumor, in the skull and near the eye, both represented areas of high lactate concentration In humans, this tumor occurs in skeletal muscle, also associated with high These include ASPSCR1–TF in all cases of alveolar soft part sarcoma (ASPS) and ASPSCR1–TF, PRCCTF, SFPQTF and others in a subset of paediatric and adult RCCs Here we examined the functional properties of the ASPSCR1–TF fusion oncoprotein, defined its target promoters on a genomewide basis and performed a highthroughput RNA Plasmid construction Nterminal FLAGtagged ASPSCR1TF was introduced into both the pMYsIRESGFP and pMYsIRESLuc vectors The fulllength ASPSCR1TF was cloned from a human ASPS case Artificial chimeric ASPSCR1 fusions between ASPSCR1 and TFEB, TFEC, or MITF were also generated by twostep PCR using primers encompassing both ASPSCR1 and
Kidney Renal Cell Carcinoma With T X 17 P11 Q25 Aspscr1 Tfe3
Alveolar Soft Part Sarcomas Molecular Pathogenesis And Implications For Novel Targeted Therapies
Human Gene TF (ENST) Description Homo sapiens transcription factor binding to IGHM enhancer 3 (TF), transcript variant 1, mRNA (from RefSeq NM_) RefSeq Summary (NM_) This gene encodes a basic helixloophelix domaincontaining transcription factor that binds MUtype Ebox sequences in the promoter of genes The ASPSCR1/TF fusion replaces the Nterminal portion of TF by the fused ASPSCR1 sequences, while retaining the TF DNAbinding domain, implicating transcriptional deregulation in the pathogenesis of ASPS Heimann et al (01) identified the ASPSCR1 gene, which they called RCC17, partnered with TF in two 5yearold Belgian girls ofQ131) Morphologically, the distinct
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A fusion partner was identified in 53/60 (%) cases, including 18 SFPQ (PSF), 16 PRCC, 12 ASPSCR1 (ASPL), 6 NONO, and 1 DVL2 We provide the first morphologic description of the NONOTF RCC, which frequently demonstrates subnuclear vacuoles leading to distinctive suprabasal nuclear palisading Based on morphologic features (nested pattern) and the above IHC results including strong TF expression, ASPS was a strong consideration Although fluorescence in situ hybridization results were positive for TF gene rearrangement, the specific TF/ASPSCR1 rearrangement (X17ASPSCR1 Tether containing UBX domain for GLUT4 ( TUG) is a protein that in humans is encoded by the ASPSCR1 gene This gene is a candidate gene for alveolar soft part sarcoma (ASPS) It has been found that ASPSCR1 can undergo oncogenic rearrangement with transcription factor TF gene, creating an aberrant gene that is a stronger
Combining Integrated Genomics And Functional Genomics To Dissect The Biology Of A Cancer Associated Aberrant Transcription Factor The Aspscr1 Tfe3 Fusion Oncoprotein Kobos 13 The Journal Of Pathology Wiley Online Library
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TFF Alveolar softpart sarcoma (ASPS) is a rare malignant tumor typically occurring in patients in their s to 30s within the muscle and deep tissues of the extremities ASPS is slow growing and refractory to chemotherapy with a propensity to metastasize Prolonged survival is possible even with metastasis, although the longterm diseaserelated mortality rate is highThe TF fusion partners in the latter three neoplasms have been fairly consistent;3 ASPSCR1 TEXT A number sign (#) is used with this entry because some cases of alveolar soft part sarcoma have been found to be caused by fusion of the ASPSCR1 () and TF () genes Description Alveolar soft part sarcoma is an unusual tumor with highly characteristic histopathology and ultrastructure
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Disease ASPSCR1/TF renal cell carcinomas harbor the same gene fusion as alveolar soft part sarcoma, but belong to the family of Xp11 translocation RCC Xp11 translocation renal cell carcinoma (RCCs) harbor gene fusions involving TF transcription factor The The t (6;11) RCCs harbor a specific MALAT1 (Alpha) TFEB gene fusionThe ASPSCR1TF fusion was originally identified in 100% of alveolar soft part sarcomas (ASPS), a rare lung cancer variant with no known RCC association, and the SFPQTF fusion and possibly other TFfusions are also found in a subset of rare tumors known as perivascular epithelioid cell neoplasms (PEComas) 27,28 The existence ofAlveolar soft part sarcoma is characterized by a der(17)(X;17)(p112;q25) translocation resulting in an ASPSCR1TF gene fusion, the distinctive epithelioid hemangioendothelioma subset harbors a t(X;11)(p112;q13) translocation resulting in a YAP1TF gene
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The recent discovery of the role of the ASPSCR1 TF fusion protein in the MET protooncogene signaling pathway promoting angiogenesis and cell proliferation offers a promising targeted molecular Introduction TFtranslocation renal cell carcinoma (TFtRCC) is a rare subtype of kidney cancer, characterized by Xp112 translocations resulting in TF fusion with various partner genes To date, more than partner genes have been identified in fusions with TF, including SFPQ, ASPSCR1, NONO, PRCC, RBM10, MED15, etc Due to the variety of partners andA conditional expression in mice of the fusion gene ASPSCR1TF from human alveolar soft part sarcoma (ASPS) generated a model that recapitulates the human tumor histologically and by expression profile
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The ASPSCR1/TF fusion replaces the Nterminal portion of TF by the fused ASPSCR1 sequences, while retaining the TF DNAbinding domain, implicating transcriptional deregulation in the pathogenesis of ASPS Ladanyi et al (01) identified major and minor splice forms of the ASPSCR1 transcript which differ by the absence or presence of a 47In RCC, TF translocation partners have been shown to include the ASPSCR1, SFPQ and NONO genes 3 Although RCC and ASPS have been shown to have identical ASPSCR1TF fusion transcripts, the t(X;17) translocation is consistently balanced in the former but usually unbalanced in the latter the derivative X chromosome is not seen in ASPS 4ASPSCR1/TF Fusion Gene In papillary renal cell carcinoma tissue from two 5yearold Belgian girls of African origin, Heimann et al (01) identified a translocation t(X;17)(p112;q25) that fused the Nterminal region of the ASPSPR1 gene to the Cterminal region of TF including the bHLH DNAbinding domain and the leucine zipper dimerization domain
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Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor of unknown histogenesis generally characterized by the der (17)t (X;17) (p112;q25) translocation which results in the ASPSCR1TF gene fusion Primary ASPS of the thyroid gland has not yet been reported During oncology followup for breast cancer, a pulmonary nodule and thyroid Tfe3 is a critical transcription factor that regulates Pgc1alpha gene expression in myotubes; ASPS is a malignant mesenchymal tumour with an ASPSCR1TF fusion molecular signature (der(17)t(X;17)(p112;q25) translocation This results in the fusion of TF transcription factor gene at Xp112 with ASPSCR1 (also known as ASPL) at 17q25 As mentioned earlier, the same gene signature is also present in a subset of RCCs, which have a
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Breakpoint for translocation to form NONOTF, PSFTF and ASPSCR1TF oncogenes 2 Keywords Disease i Protooncogene Organismspecific databases DisGeNET i 7030 MalaCards i TF OpenTargets i ENSG Orphanet i , Alveolar soft tissue sarcoma This translocation results in the chimeric ASPSCR1TF transcription factor which drives tumorigenesis Complete surgical resection is crucial in allowing a successful outcome in these cases Here, we describe an 11monthold female infant who presented with a wellcircumscribed lesion of the tongue, with the clinical and radiologicTF Overexpression of TF is a sensitive and specific marker of Xp11 translocation in renal cell carcinomas TF is also expressed in alveolar soft part sarcoma the hallmark of which is a chromosomal rearrangement at 17q25 and Xp112 engendering an ASPSCR1–TF fusion gene Use of this antibody is an aid in the recognition of Xp11
Molecular Landscape In Alveolar Soft Part Sarcoma Implications For Molecular Targeted Therapy Sciencedirect
Combining Integrated Genomics And Functional Genomics To Dissect The Biology Of A Cancer Associated Aberrant Transcription Factor The Aspscr1 Tfe3 Fusion Oncoprotein Kobos 13 The Journal Of Pathology Wiley Online Library
Soft Tissues Alveolar soft part sarcoma with t (X;17) (p11;q25) ASPSCR1TF The histogenesis of this tumour is still unknown, despite immunohistochemestry studies and electron microscopy It may have a myogenic origin, and might be a variant of rhabdomyosarcoma Rare tumour represents less than 1% of soft tissues sarcomas of adults and 12 YAP1TFfused hemangioendothelioma is an extremely rare malignant vascular tumor, with only a few dozen cases reported, most of which were single case reports or larger case series that combineASPSCR1TF alveolar soft part sarcoma Pubmed 17 ASPSCR1TF ASPSCR1TF Adenocarcinoma, Alveolar soft part sarcoma, renal cell carcinoma Pubmed
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A total of five TF gene fusions (PRCCTF, ASPSCR1TF, SFPQTF, NONOTF, and CLTCTF) and one TFEB gene fusion (MALAT1TFEB) have been identified in RCC tumours and characterized at the mRNA transcript level A multitude of molecular pathways welldescribed in carcinogenesis are regulated in part by TF or TFEB proteins, including
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Marc Ladanyi Yes Most Alveolar Soft Part Sarcomas Aspscr1 Tfe3 Fusion Would Be Considered To Fall In The Simple Reciprocal Translocation Group Blast From The Past Some Of Our Work
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