Soft Tissues: Angiomatoid fibrous histiocytoma with t(12;22)(q13;q12) EWSR1/ATF1

2009-06-01   Jean-Loup Huret  

1.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 IDYearTitleCitations
397694572024EWSR1::ATF1 Translocation: A Common Tumor Driver of Distinct Human Neoplasms.142
354777132022EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.71
245954182014Envisioning the next WHO head and neck classification.69
380673002023The Role of Gene Fusions in Thymic Epithelial Tumors.67
381362962023EWSR1::ATF1 Orchestrates the Clear Cell Sarcoma Transcriptome in Human Tumors and a Mouse Genetic Model.56
352006082022A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases.55
374051232023Targeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene EWSR1::ATF1 by HDAC Inhibition.54
351183102021Sarcomas of the mediastinum with epithelioid morphology.51
360416322022Protein arginine methyltransferase 5 is essential for oncogene product EWSR1-ATF1-mediated gene transcription in clear cell sarcoma.47
285050042017A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.46
384214622024Primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion: a literature review.46
400047642025Clear Cell Sarcoma (CCS) of the Soft Tissue: An Update Narrative Review with Emphasis on the Utility of PRAME in Differential Diagnosis.46
382915292024Potential prognostic determinants for FET::CREB fusion-positive intracranial mesenchymal tumor.45
341939432021Generation of human embryonic stem cell models to exploit the EWSR1-CREB fusion promiscuity as a common pathway of transformation in human tumors.43
383891012024Pulmonary salivary gland tumor-hyalinizing clear cell carcinoma: a literature review.42
331414882021Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms.39
341569762021The clear cell sarcoma functional genomic landscape.39
338270332021Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma.38
350946982022Clinicopathological 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
390312002024EWSR1::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
364059392022A rare case of clear cell sarcoma of the foot with a cascade of pathological misdiagnosis-the importance of expert sarcoma pathology.31
388835142024Diagnostic Utility of EWSR1 in Clear Cell Odontogenic Carcinoma: A Systematic Review.28
348214262022Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.27
384298272024Re-evaluating a historic cohort of sinonasal and skull base mucoepidermoid carcinoma: an institutional experience.25
238212182013Hyalinizing clear cell carcinoma of salivary gland: a review and update.24
234598382013What the EWSR1-ATF1 fusion has taught us about hyalinizing clear cell carcinoma.23
353462552022Primary lung hyalinizing clear cell carcinoma: a diagnostic challenge in biopsy.22
328162312021Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature.19
342515952022Clear Cell Carcinoma in the Oral Cavity with Three Novel Types of EWSR1-ATF1 Translocation: A Case Report.18
302190842018Detection 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
341215092021Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients.17
300470652019Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1.17
317821192020Clear Cell Odontogenic Carcinoma Harboring the EWSR1-ATF1 Fusion Gene: Report of a Rare Case.16
370973472023CREB 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
333357312021Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report.13
306428522019Atypical central neurocytoma with novel EWSR1-ATF1 fusion and MUTYH mutation detected by next-generation sequencing.8
347660642021Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report.7
334054002021Molecular Pathology of Salivary Gland Neoplasms: Diagnostic, Prognostic, and Predictive Perspective.0
225107622012Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status.0
180944132007EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.0
354667252023Primary Pulmonary Myxoid Sarcoma with EWSR1::ATF1 Fusion: A Case Report.0
372583302023Primary angiomatoid fibrous histiocytoma of the mandible with EWSR1-ATF1 fusion in an adult patient: case report and review of literature.0
195615682009Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts).0
360766732022Intracranial Myxoid Mesenchymal Tumour with EWSR1-ATF1 Fusion Sans Myxoid Stroma - Report of A Newer Entity with Brief Review of Literature.0
367912512023Inflammatory and Nested Testicular Sex Cord Tumor: A Novel Neoplasm With Aggressive Clinical Behavior and Frequent EWSR1::ATF1 Gene Fusions.0
320163222020Intracranial Myxoid Mesenchymal Tumor With EWSR1-ATF1 Fusion.0
351650592022Detection of EWSR1 fusions in CCOC by targeted RNA-seq.0
364700432023Maxillary clear cell odontogenic carcinoma with EWSR1-ATF1 fusion gene mimicking sclerosing odontogenic carcinoma: A case report and literature review.0
259271512015Angiomatoid fibrous histiocytoma: the current status of pathology and genetics.0
380182622024Current diagnosis and treatment of salivary gland-type tumors of the lung.0
369348612023Extraenteric Malignant Gastrointestinal Neuroectodermal Tumor-A Clinicopathologic and Molecular Genetic Study of 11 Cases.0
346863982022Clear cell carcinoma: a comprehensive literature review of 254 cases.0
352670842022The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls.0
336839842021EWSR1-ATF1 Fusion in a Myoepithelial Carcinoma of Soft Tissue With Small Round Cell Morphology: A Potential Diagnostic Pitfall.0
257240382015Clear cell sarcoma-like tumor of the gastrointestinal tract: an evolving entity.0
285590202017Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.0
326830052020Adult Intracranial Myxoid Mesenchymal Tumor with EWSR1-ATF1 Gene Fusion.0
259903692016Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.0
272538492016Biology and management of clear cell sarcoma: state of the art and future perspectives.0
158840992005Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma.0
214849322011EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland.0
308238612019Primary Adrenal Angiomatoid Fibrous Histiocytoma With Novel EWSR1-ATF1 Gene Fusion Exon-Exon Breakpoint.0
308195302019Paraneoplastic disorders associated with miscellaneous neoplasms with focus on selected soft tissue and Undifferentiated/ rhabdoid malignancies.0
385213732024Back to the future! Selected bone and soft tissue neoplasms with shared genetic alterations but differing morphological and immunohistochemical phenotypes.0
340493182022Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases.0
228864382012Clear cell sarcoma expressing a novel chimerical transcript EWSR1 exon 7/ATF1 exon 6.0
349191832022[Mesenchymal tumors and tumor-like lesions of the gastrointestinal tract: an overview].0
290768772018The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.0
243783902014Promiscuous genes involved in recurrent chromosomal translocations in soft tissue tumours.0
330270732021Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1 Rearrangement Identifies Frequent PLAG1 Gene Fusions But No EWSR1 Fusion Transcripts.0
271506762016Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: The current nomenclature, clinical/pathological characteristics and management.0
374791382023Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland.0
225880662012Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1-CREB1 and EWSR1-ATF1 fusions.0
258042552015Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities.0
239535912013A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site.0
275260142016[New developments in molecular diagnostics of carcinomas of the salivary glands: "translocation carcinomas"].0
365917182022Primary pulmonary hyalinising clear cell carcinoma: Two cases and literature review.0
172271182007Clear cell sarcoma of tendons and aponeuroses: a review.0
177247452007EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma.0
252681962014Clear cell melanoma: a cutaneous clear cell malignancy.0
263639992015[Angiomatoid fibrous histiocytoma in children: 6 cases].0
299702522018Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review.0
232528712012Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature.0
350398972022Malignant gastrointestinal neuroectodermal tumor in head and neck: two challenging cases with diverse morphology and different considerations for differential diagnosis.0
362888762022Establishment and Characterisation of Human Clear Cell Sarcoma and Malignant Melanoma Cell Lines.0
170752942006Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity.0
355785462023Recurring Clear Cell Odontogenic Carcinoma Involving Vertebra and Pleura: A Case Report and Literature Review.0
221540502012EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report.0
349296032022Myoepithelial and oral intracranial myxoid mesenchymal tumor-like neoplasms as diagnostic considerations of the ever-expanding extracranial myxocollagenous tumors harboring FET-CREB fusions.0
373771242023Clinical and Histopathologic Analyses of Nasopharyngeal Hyalinizing Clear Cell Carcinoma: A Series of 26 Cases With Molecular Confirmation.0
279166242017Primary paranasal sinus clear cell carcinoma with EWSR1-ATF1 fusion: report of 2 molecularly confirmed cases exhibiting unique histopathology.0
289271642017Hyalinizing Clear Cell Carcinoma of the Lung: Case Report and Review of the Literature.0
344056052021[Clinicopathological features and molecular genetic changes of lung salivary gland-type clear cell carcinoma].0
310508442019EWSR1 translocation in primary hyalinising clear cell carcinoma of the thymus.0
268620222016Hyalinizing Clear Cell Carcinoma with Biopsy-Proven Spinal Metastasis: Case Report and Review of Literature.0
253596012015Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses.0
278981922017Reappraising hyalinizing clear cell carcinoma: A population-based study with molecular confirmation.0
377156452024Metastatic 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
291434322018Primary myxoid mesenchymal tumour with intracranial location: report of a case with a EWSR1-ATF1 fusion.0
289307522018Salivary Gland Neoplasms: Does Morphological Diversity Reflect Tumor Heterogeneity.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
177247452007EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma.Antonescu CR et al
183008002008Primary 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
171884282007Fusion genes in angiomatoid fibrous histiocytoma.Hallor KH et al
180944132007EWSR1-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/soft-tissues-angiomatoid-fibrous-histiocytoma-with-t(12;22)(q13;q12)-ewsr1-atf1