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
280096022017EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location.36
290768772018The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.34
259271512015Angiomatoid fibrous histiocytoma: the current status of pathology and genetics.28
285050042017A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.24
257240382015Clear cell sarcoma-like tumor of the gastrointestinal tract: an evolving entity.17
299752502018Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion: Report of 3 Cases.16
327701232020EWSR1/FUS-CREB fusions define a distinctive malignant epithelioid neoplasm with predilection for mesothelial-lined cavities.15
313052682019Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion.14
299702522018Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review.12
272538492016Biology and management of clear cell sarcoma: state of the art and future perspectives.12
331414882021Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms.11
277648302016Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion.11
291434322018Primary myxoid mesenchymal tumour with intracranial location: report of a case with a EWSR1-ATF1 fusion.10
330270732021Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1 Rearrangement Identifies Frequent PLAG1 Gene Fusions But No EWSR1 Fusion Transcripts.9
320163222020Intracranial Myxoid Mesenchymal Tumor With EWSR1-ATF1 Fusion.9
300470652019Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1.9
259903692016Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.9
261631852015An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma.9
334054002021Molecular Pathology of Salivary Gland Neoplasms: Diagnostic, Prognostic, and Predictive Perspective.8
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.7
277698712017Reevaluation of MAML2 fusion-negative mucoepidermoid carcinoma: a subgroup being actually hyalinizing clear cell carcinoma of the salivary gland with EWSR1 translocation.7
255431602015Primary pulmonary hyalinizing clear cell carcinoma of bronchial submucosal gland origin.7
253596012015Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses.7
326830052020Adult Intracranial Myxoid Mesenchymal Tumor with EWSR1-ATF1 Gene Fusion.6
312329352019Clinical application of RNA sequencing in sarcoma diagnosis: An institutional experience.6
294910752018Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: Clinical Outcome and Pathologic Features of a Molecularly Characterized Tertiary Center Case Series.6
287454312017Trabectedin is a promising antitumor agent potentially inducing melanocytic differentiation for clear cell sarcoma.6
273465702016Oncocytic variant of malignant gastrointestinal neuroectodermal tumor: a potential diagnostic pitfall.6
271506762016Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: The current nomenclature, clinical/pathological characteristics and management.6
258042552015Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities.6
317821192020Clear Cell Odontogenic Carcinoma Harboring the EWSR1-ATF1 Fusion Gene: Report of a Rare Case.5
327735302020Primary Pulmonary Myxoid Sarcoma and Myxoid Angiomatoid Fibrous Histiocytoma: A Unifying Continuum With Shared and Distinct Features.4
310508442019EWSR1 translocation in primary hyalinising clear cell carcinoma of the thymus.4
290768742018Clear Cell Carcinoma of Salivary Glands Is Frequently p16 Positive: A Pitfall in the Interpretation of Oropharyngeal Biopsies.4
289307522018Salivary Gland Neoplasms: Does Morphological Diversity Reflect Tumor Heterogeneity.4
289469102017Primary paranasal sinus hyalinizing clear cell carcinoma: a case report.4
285590202017Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.4
289271642017Hyalinizing Clear Cell Carcinoma of the Lung: Case Report and Review of the Literature.4
271093162016Whole-exome sequencing identifies a somatic missense mutation of NBN in clear cell sarcoma of the salivary gland.4
341215092021Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients.3
330059822021Clear cell sarcoma-like/malignant gastrointestinal neuroectodermal tumor of the tongue: a clinicopathologic and molecular case report.3
328162312021Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature.3
279166242017Primary paranasal sinus clear cell carcinoma with EWSR1-ATF1 fusion: report of 2 molecularly confirmed cases exhibiting unique histopathology.3
278981922017Reappraising hyalinizing clear cell carcinoma: A population-based study with molecular confirmation.3
340493182022Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases.2
345098982021Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls.2
334627432021Clear cell tumor with melanocytic differentiation and MITF-CREM translocation: a novel entity similar to clear cell sarcoma.2
341939432021Generation of human embryonic stem cell models to exploit the EWSR1-CREB fusion promiscuity as a common pathway of transformation in human tumors.2
338270332021Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma.2
333357312021Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report.2
308238612019Primary Adrenal Angiomatoid Fibrous Histiocytoma With Novel EWSR1-ATF1 Gene Fusion Exon-Exon Breakpoint.2
294343412018Hyalinizing clear cell carcinoma of the bronchial glands: presentation of three cases and pathological comparisons with salivary gland counterparts and bronchial mucoepidermoid carcinomas.2
276371572016'Pure' spindle cell variant of angiomatoid fibrous histiocytoma, lacking classic histologic features.2
256935742015Soft tissue myoepithelial carcinoma with rhabdoid-like features and EWSR1 rearrangement: Fine needle aspiration cytology with histologic correlation.2
346863982022Clear cell carcinoma: a comprehensive literature review of 254 cases.1
348214262022Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.1
342515952022Clear Cell Carcinoma in the Oral Cavity with Three Novel Types of EWSR1-ATF1 Translocation: A Case Report.1
354667252022Primary Pulmonary Myxoid Sarcoma with EWSR1::ATF1 Fusion: A Case Report.1
336168522021Clear Cell Odontogenic Carcinoma: First Report of Novel EWSR1-CREM Fusion Gene in Case of Long-Term Misdiagnosis.1
345409142021Malignant Gastrointestinal Neuroectodermal Tumor in the Right Heart: A Report of an Extremely Rare Case Presenting With a Cardiac Mass.1
341569762021The clear cell sarcoma functional genomic landscape.1
336839842021EWSR1-ATF1 Fusion in a Myoepithelial Carcinoma of Soft Tissue With Small Round Cell Morphology: A Potential Diagnostic Pitfall.1
334325312021Intracranial angiomatoid fibrous histiocytoma with rhabdoid features: a mimic of rhabdoid meningioma.1
338289952021Molecular Characteristics of Genes and the Immune Microenvironment of a Rare Chest Malignant Tumor (Pulmonary Clear Cell Sarcoma): A Case Report.1
334784362021Primary clear cell sarcoma of the femur: a unique case with RT-PCR and direct sequencing confirmation of EWSR1/ATF1 fusion gene.1
315672752020SOX9 Immunohistochemistry in the Distinction of Angiomatoid Fibrous Histiocytoma From Histologic Mimics: Diagnostic Utility and Pitfalls.1
312762792019A case report of cutaneous melanocytoma with CRTC1-TRIM11 fusion: Is CMCT distinct from clear cell sarcoma of soft tissue?1
308195302019Paraneoplastic disorders associated with miscellaneous neoplasms with focus on selected soft tissue and Undifferentiated/ rhabdoid malignancies.1
305548332019[Clear cell sarcoma or gastrointestinal neuroectodermal tumor (GNET) of the tongue? Case report and review of the literature of an extremely rare tumor localization].1
306428522019Atypical central neurocytoma with novel EWSR1-ATF1 fusion and MUTYH mutation detected by next-generation sequencing.1
302938902018[Angiomatoid fibrous histiocytoma of the radial pulse groove].1
301772202018Oral malignant gastrointestinal neuroectodermal tumour with junctional component mimicking mucosal melanoma.1
301941472018Establishment and Characterization of a Novel Human Clear-cell Sarcoma of Soft-tissue Cell Line, RSAR001, Derived from Pleural Effusion of a Patient with Pleural Dissemination.1
291366862017[Clinicopathologic and molecular characteristics of malignant gastrointestinal neuroectodermal tumors].1
268620222016Hyalinizing Clear Cell Carcinoma with Biopsy-Proven Spinal Metastasis: Case Report and Review of Literature.1
263639992015[Angiomatoid fibrous histiocytoma in children: 6 cases].1
357301862022Brain parenchymal angiomatoid fibrous histiocytoma and spinal myxoid mesenchymal tumor with FET: CREB fusion, a spectrum of the same tumor type.0
351650592022Detection of EWSR1 fusions in CCOC by targeted RNA-seq.0
350398972022Malignant gastrointestinal neuroectodermal tumor in head and neck: two challenging cases with diverse morphology and different considerations for differential diagnosis.0
352670842022The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls.0
357176812022Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network.0
355785462022Recurring Clear Cell Odontogenic Carcinoma Involving Vertebra and Pleura: A Case Report and Literature Review.0
353462552022Primary lung hyalinizing clear cell carcinoma: a diagnostic challenge in biopsy.0
354777132022EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.0
354337132022Hyalinizing Clear Cell Salivary Gland Carcinoma of the Epipharynx: A Minor Salivary/Tubarial Gland Malignancy.0
349191832022[Mesenchymal tumors and tumor-like lesions of the gastrointestinal tract: an overview].0
352006082022A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases.0
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.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
347660642021Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report.0
344056052021[Clinicopathological features and molecular genetic changes of lung salivary gland-type clear cell carcinoma].0
335993022021Clear cell sarcoma of soft tissue with eccrine differentiation: A case report and review of the literature.0
327200342021Does Nodal Metastasis and Perineural Invasion Affect Local Control in Hyalinizing Clear Cell Carcinoma of the Oral Cavity? A Case Report with Long Term Follow-Up.0
351183102021Sarcomas of the mediastinum with epithelioid morphology.0
326400782021Salivary gland hyalinizing clear-cell carcinoma with cutaneous metastasis: A rare and deceptive tumor.0
333919502020Superficial Clear Cell Sarcoma (Melanoma of Soft Parts) of the Large toe in an 80-Year-Old Female With a Rare Cytogenetic Translocation.0
333442762020Hyalinizing clear cell carcinoma of the soft palate: a review of literature review.0
275260142016[New developments in molecular diagnostics of carcinomas of the salivary glands: "translocation carcinomas"].0
265860172015[Gastro-intestinal neuroectodermal tumor (GNET): A case report of a small intestine tumor with hepatic metastases].0
256713612015[Small cell type (Ewing-like) clear cell sarcoma of soft parts: a case report].0

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