Soft Tissues: Angiomatoid fibrous histiocytoma with t(12;22)(q13;q12) EWSR1/ATF1
2009-06-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Epidemiology
Six cases of angiomatoid fibrous histiocytoma with a t(12;22)(q13;q12) have so far been described; there were 4 male and 2 female patients, aged 9, 10, 11, 25, 26, and 79 years (Hallor et al., 2005; Antonescu et al., 2007; Hallor et al., 2007; Rossi et al., 2007; Dunham et al., 2008).
Pathology
Cases seemed to have presented a spindle morphology preferentially, but data is too scarce.
Cytogenetics
Cytogenetics morphological
The t(12;22)(q13;q12), as well as the t(12;16)(q13;p11) (5 FUS - 3 ATF1), are rarer than the t(2;22)(q34;q12) (5 EWSR1 - 3 CREB1) in angiomatoid fibrous histiocytoma.
Genes Involved and Proteins
Gene name
ATF1 (activating transcription factor 1)
Location
12q13.12
Protein description
Contains a KID domain (kinase inductible domain), a basic motif (DNA binding) and a leucine-zipper for dimerization, like CREB1. DNA binding protein, binds the consensus sequence: 5GTGACGT(A/C)(A/G)-3. Transcription factor.
Gene name
EWSR1 (Ewing sarcoma breakpoint region 1)
Location
22q12.2
Protein description
From N-term to C-term: a transactivation domain (TAD) containing multiple degenerate hexapeptide repeats, 3 arginine/glycine rich domains (RGG regions), a RNA recognition motif, and a RanBP2 type Zinc finger. Role in transcriptional regulation for specific genes and in mRNA splicing.
Result of the chromosomal anomaly
Description
5 EWSR1 - 3 ATF1. EWSR1 exon 7 is fused in frame to ATF1 exon 5 in all but one case, where EWSR1 exon 8 was fused in frame to ATF1 exon 4.
Description
Fusion of the N terminal transactivation domain of EWSR1 to the DNA binding domain of ATF1.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 39769457 | 2024 | EWSR1::ATF1 Translocation: A Common Tumor Driver of Distinct Human Neoplasms. | 142 |
| 35477713 | 2022 | EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma. | 71 |
| 24595418 | 2014 | Envisioning the next WHO head and neck classification. | 69 |
| 38067300 | 2023 | The Role of Gene Fusions in Thymic Epithelial Tumors. | 67 |
| 38136296 | 2023 | EWSR1::ATF1 Orchestrates the Clear Cell Sarcoma Transcriptome in Human Tumors and a Mouse Genetic Model. | 56 |
| 35200608 | 2022 | A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases. | 55 |
| 37405123 | 2023 | Targeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene EWSR1::ATF1 by HDAC Inhibition. | 54 |
| 35118310 | 2021 | Sarcomas of the mediastinum with epithelioid morphology. | 51 |
| 36041632 | 2022 | Protein arginine methyltransferase 5 is essential for oncogene product EWSR1-ATF1-mediated gene transcription in clear cell sarcoma. | 47 |
| 28505004 | 2017 | A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions. | 46 |
| 38421462 | 2024 | Primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion: a literature review. | 46 |
| 40004764 | 2025 | Clear Cell Sarcoma (CCS) of the Soft Tissue: An Update Narrative Review with Emphasis on the Utility of PRAME in Differential Diagnosis. | 46 |
| 38291529 | 2024 | Potential prognostic determinants for FET::CREB fusion-positive intracranial mesenchymal tumor. | 45 |
| 34193943 | 2021 | Generation of human embryonic stem cell models to exploit the EWSR1-CREB fusion promiscuity as a common pathway of transformation in human tumors. | 43 |
| 38389101 | 2024 | Pulmonary salivary gland tumor-hyalinizing clear cell carcinoma: a literature review. | 42 |
| 33141488 | 2021 | Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms. | 39 |
| 34156976 | 2021 | The clear cell sarcoma functional genomic landscape. | 39 |
| 33827033 | 2021 | Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma. | 38 |
| 35094698 | 2022 | Clinicopathological and molecular study of 10 salivary gland clear cell carcinomas, with emphasis on rare cases with high grade transformation and occurring in uncommon sites. | 36 |
| 39031200 | 2024 | EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms. | 34 |
| 36405939 | 2022 | A rare case of clear cell sarcoma of the foot with a cascade of pathological misdiagnosis-the importance of expert sarcoma pathology. | 31 |
| 38883514 | 2024 | Diagnostic Utility of EWSR1 in Clear Cell Odontogenic Carcinoma: A Systematic Review. | 28 |
| 34821426 | 2022 | Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas. | 27 |
| 38429827 | 2024 | Re-evaluating a historic cohort of sinonasal and skull base mucoepidermoid carcinoma: an institutional experience. | 25 |
| 23821218 | 2013 | Hyalinizing clear cell carcinoma of salivary gland: a review and update. | 24 |
| 23459838 | 2013 | What the EWSR1-ATF1 fusion has taught us about hyalinizing clear cell carcinoma. | 23 |
| 35346255 | 2022 | Primary lung hyalinizing clear cell carcinoma: a diagnostic challenge in biopsy. | 22 |
| 32816231 | 2021 | Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature. | 19 |
| 34251595 | 2022 | Clear Cell Carcinoma in the Oral Cavity with Three Novel Types of EWSR1-ATF1 Translocation: A Case Report. | 18 |
| 30219084 | 2018 | Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor. | 18 |
| 34121509 | 2021 | Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients. | 17 |
| 30047065 | 2019 | Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1. | 17 |
| 31782119 | 2020 | Clear Cell Odontogenic Carcinoma Harboring the EWSR1-ATF1 Fusion Gene: Report of a Rare Case. | 16 |
| 37097347 | 2023 | CREB fusion-associated epithelioid mesenchymal neoplasms of the female adnexa: three cases documenting a novel location of an emerging entity and further highlighting an ambiguous misleading immunophenotype. | 15 |
| 33335731 | 2021 | Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report. | 13 |
| 30642852 | 2019 | Atypical central neurocytoma with novel EWSR1-ATF1 fusion and MUTYH mutation detected by next-generation sequencing. | 8 |
| 34766064 | 2021 | Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report. | 7 |
| 33405400 | 2021 | Molecular Pathology of Salivary Gland Neoplasms: Diagnostic, Prognostic, and Predictive Perspective. | 0 |
| 22510762 | 2012 | Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. | 0 |
| 18094413 | 2007 | EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. | 0 |
| 35466725 | 2023 | Primary Pulmonary Myxoid Sarcoma with EWSR1::ATF1 Fusion: A Case Report. | 0 |
| 37258330 | 2023 | Primary angiomatoid fibrous histiocytoma of the mandible with EWSR1-ATF1 fusion in an adult patient: case report and review of literature. | 0 |
| 19561568 | 2009 | Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). | 0 |
| 36076673 | 2022 | Intracranial Myxoid Mesenchymal Tumour with EWSR1-ATF1 Fusion Sans Myxoid Stroma - Report of A Newer Entity with Brief Review of Literature. | 0 |
| 36791251 | 2023 | Inflammatory and Nested Testicular Sex Cord Tumor: A Novel Neoplasm With Aggressive Clinical Behavior and Frequent EWSR1::ATF1 Gene Fusions. | 0 |
| 32016322 | 2020 | Intracranial Myxoid Mesenchymal Tumor With EWSR1-ATF1 Fusion. | 0 |
| 35165059 | 2022 | Detection of EWSR1 fusions in CCOC by targeted RNA-seq. | 0 |
| 36470043 | 2023 | Maxillary clear cell odontogenic carcinoma with EWSR1-ATF1 fusion gene mimicking sclerosing odontogenic carcinoma: A case report and literature review. | 0 |
| 25927151 | 2015 | Angiomatoid fibrous histiocytoma: the current status of pathology and genetics. | 0 |
| 38018262 | 2024 | Current diagnosis and treatment of salivary gland-type tumors of the lung. | 0 |
| 36934861 | 2023 | Extraenteric Malignant Gastrointestinal Neuroectodermal Tumor-A Clinicopathologic and Molecular Genetic Study of 11 Cases. | 0 |
| 34686398 | 2022 | Clear cell carcinoma: a comprehensive literature review of 254 cases. | 0 |
| 35267084 | 2022 | The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls. | 0 |
| 33683984 | 2021 | EWSR1-ATF1 Fusion in a Myoepithelial Carcinoma of Soft Tissue With Small Round Cell Morphology: A Potential Diagnostic Pitfall. | 0 |
| 25724038 | 2015 | Clear cell sarcoma-like tumor of the gastrointestinal tract: an evolving entity. | 0 |
| 28559020 | 2017 | Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene. | 0 |
| 32683005 | 2020 | Adult Intracranial Myxoid Mesenchymal Tumor with EWSR1-ATF1 Gene Fusion. | 0 |
| 25990369 | 2016 | Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker. | 0 |
| 27253849 | 2016 | Biology and management of clear cell sarcoma: state of the art and future perspectives. | 0 |
| 15884099 | 2005 | Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. | 0 |
| 21484932 | 2011 | EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. | 0 |
| 30823861 | 2019 | Primary Adrenal Angiomatoid Fibrous Histiocytoma With Novel EWSR1-ATF1 Gene Fusion Exon-Exon Breakpoint. | 0 |
| 30819530 | 2019 | Paraneoplastic disorders associated with miscellaneous neoplasms with focus on selected soft tissue and Undifferentiated/ rhabdoid malignancies. | 0 |
| 38521373 | 2024 | Back to the future! Selected bone and soft tissue neoplasms with shared genetic alterations but differing morphological and immunohistochemical phenotypes. | 0 |
| 34049318 | 2022 | Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases. | 0 |
| 22886438 | 2012 | Clear cell sarcoma expressing a novel chimerical transcript EWSR1 exon 7/ATF1 exon 6. | 0 |
| 34919183 | 2022 | [Mesenchymal tumors and tumor-like lesions of the gastrointestinal tract: an overview]. | 0 |
| 29076877 | 2018 | The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas. | 0 |
| 24378390 | 2014 | Promiscuous genes involved in recurrent chromosomal translocations in soft tissue tumours. | 0 |
| 33027073 | 2021 | Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1 Rearrangement Identifies Frequent PLAG1 Gene Fusions But No EWSR1 Fusion Transcripts. | 0 |
| 27150676 | 2016 | Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: The current nomenclature, clinical/pathological characteristics and management. | 0 |
| 37479138 | 2023 | Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland. | 0 |
| 22588066 | 2012 | Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1-CREB1 and EWSR1-ATF1 fusions. | 0 |
| 25804255 | 2015 | Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities. | 0 |
| 23953591 | 2013 | A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site. | 0 |
| 27526014 | 2016 | [New developments in molecular diagnostics of carcinomas of the salivary glands: "translocation carcinomas"]. | 0 |
| 36591718 | 2022 | Primary pulmonary hyalinising clear cell carcinoma: Two cases and literature review. | 0 |
| 17227118 | 2007 | Clear cell sarcoma of tendons and aponeuroses: a review. | 0 |
| 17724745 | 2007 | EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. | 0 |
| 25268196 | 2014 | Clear cell melanoma: a cutaneous clear cell malignancy. | 0 |
| 26363999 | 2015 | [Angiomatoid fibrous histiocytoma in children: 6 cases]. | 0 |
| 29970252 | 2018 | Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review. | 0 |
| 23252871 | 2012 | Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature. | 0 |
| 35039897 | 2022 | Malignant gastrointestinal neuroectodermal tumor in head and neck: two challenging cases with diverse morphology and different considerations for differential diagnosis. | 0 |
| 36288876 | 2022 | Establishment and Characterisation of Human Clear Cell Sarcoma and Malignant Melanoma Cell Lines. | 0 |
| 17075294 | 2006 | Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity. | 0 |
| 35578546 | 2023 | Recurring Clear Cell Odontogenic Carcinoma Involving Vertebra and Pleura: A Case Report and Literature Review. | 0 |
| 22154050 | 2012 | EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report. | 0 |
| 34929603 | 2022 | Myoepithelial and oral intracranial myxoid mesenchymal tumor-like neoplasms as diagnostic considerations of the ever-expanding extracranial myxocollagenous tumors harboring FET-CREB fusions. | 0 |
| 37377124 | 2023 | Clinical and Histopathologic Analyses of Nasopharyngeal Hyalinizing Clear Cell Carcinoma: A Series of 26 Cases With Molecular Confirmation. | 0 |
| 27916624 | 2017 | Primary paranasal sinus clear cell carcinoma with EWSR1-ATF1 fusion: report of 2 molecularly confirmed cases exhibiting unique histopathology. | 0 |
| 28927164 | 2017 | Hyalinizing Clear Cell Carcinoma of the Lung: Case Report and Review of the Literature. | 0 |
| 34405605 | 2021 | [Clinicopathological features and molecular genetic changes of lung salivary gland-type clear cell carcinoma]. | 0 |
| 31050844 | 2019 | EWSR1 translocation in primary hyalinising clear cell carcinoma of the thymus. | 0 |
| 26862022 | 2016 | Hyalinizing Clear Cell Carcinoma with Biopsy-Proven Spinal Metastasis: Case Report and Review of Literature. | 0 |
| 25359601 | 2015 | Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses. | 0 |
| 27898192 | 2017 | Reappraising hyalinizing clear cell carcinoma: A population-based study with molecular confirmation. | 0 |
| 37715645 | 2024 | Metastatic Testicular Sex Cord Tumor Harboring a EWSR1::ATF1 Gene Fusion-A Case Report of a Novel Neoplasm: "Inflammatory and Nested Testicular Sex Cord Tumor". | 0 |
| 29143432 | 2018 | Primary myxoid mesenchymal tumour with intracranial location: report of a case with a EWSR1-ATF1 fusion. | 0 |
| 28930752 | 2018 | Salivary Gland Neoplasms: Does Morphological Diversity Reflect Tumor Heterogeneity. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17724745 | 2007 | EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. | Antonescu CR et al |
| 18300800 | 2008 | Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes. | Dunham C et al |
| 17188428 | 2007 | Fusion genes in angiomatoid fibrous histiocytoma. | Hallor KH et al |
| 18094413 | 2007 | EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. | Rossi S et al |
Citation
Jean-Loup Huret
Soft Tissues: Angiomatoid fibrous histiocytoma with t(12;22)(q13;q12) EWSR1/ATF1
Atlas Genet Cytogenet Oncol Haematol. 2009-06-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/6286
