Spindle and Round Cell Sarcoma With EWSR1-PATZ1 Gene Fusion

Chougule, Abhijit; Taylor, Martin S.; Nardi, Valentina; Chebib, Ivan; Coté, Gregory M.; Choy, Edwin; Nielsen, G. Petur; Deshpande, Vikram

doi:10.1097/pas.0000000000001183

Cited by 65 publications

(50 citation statements)

References 33 publications

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“…As previously mentioned, these tumors can have a desmoplastic stroma and show polyphenotypic differentiation with desmin positivity, and would also be positive for EWSR1 gene rearrangement by break‐apart FISH. Intra‐abdominal sarcomas with EWSR1 ‐ PATZ1 gene fusion have also shown similar histologic features and immunostaining results, and similarly would show an EWSR1 rearrangement by break‐apart FISH .…”

Section: Discussionmentioning

confidence: 73%

“…Desmin positivity, in the context of a polyphenotypic immunoprofile and particularly if there is a globular staining pattern , is highly suggestive of a DSRCT diagnosis. However, a polyphenotypic immuneprofile with desmin positivity is not specific to DSRCT, and can also be encountered in angiomatous fibrous histiocytoma, intracranial myxoid mesenchymal tumors and sarcomas with EWSR1‐PATZ1 gene fusion . We encountered two such cases while establishing our DSRCT study cohort, which were desmin‐positive but demonstrated an EWSR1‐ATF1 gene fusion on molecular evaluation, one of these cases also had a prominent desmoplastic stroma.…”

Section: Discussionmentioning

confidence: 96%

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Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

et al. 2019

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Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra‐abdominally, and are defined by EWSR1‐WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion‐positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6–25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma‐like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1‐WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1‐WT1 fusion provides a definitive diagnosis of DSRCT. Genome‐wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 96%

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

et al. 2019

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“…Chromosome 22specific inversions that translocate the transcription factor EWSR1 with PATZ1 have been observed in various sarcomas. While EWSR1 translocates with ETS family proteins in Ewing's sarcoma, it potentially encodes two fusion proteins EWSR1-PATZ1 and PATZ1-EWSR1, the latter of which will contain the BTB domain (Siegfried et al, 2019;Bridge et al, 2019;Chougule et al, 2019;Sankar & Lessnick, 2011;Mastrangelo et al, 2000;Im et al, 2000). The dimerization and co-repressor interaction properties of PATZ1 identified in this study may shed light on the mechanism of these sarcomas.…”

Section: Discussionmentioning

confidence: 99%

Structural analysis of the PATZ1 BTB domain homodimer

Piepoli

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et al. 2020

Acta Cryst Sect D Struct Biol

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PATZ1 is a ubiquitously expressed transcriptional repressor belonging to the ZBTB family that is functionally expressed in T lymphocytes. PATZ1 targets the CD8 gene in lymphocyte development and interacts with the p53 protein to control genes that are important in proliferation and in the DNA-damage response. PATZ1 exerts its activity through an N-terminal BTB domain that mediates dimerization and co-repressor interactions and a C-terminal zincfinger motif-containing domain that mediates DNA binding. Here, the crystal structures of the murine and zebrafish PATZ1 BTB domains are reported at 2.3 and 1.8 Å resolution, respectively. The structures revealed that the PATZ1 BTB domain forms a stable homodimer with a lateral surface groove, as in other ZBTB structures. Analysis of the lateral groove revealed a large acidic patch in this region, which contrasts with the previously resolved basic co-repressor binding interface of BCL6. A large 30-amino-acid glycine-and alanine-rich central loop, which is unique to mammalian PATZ1 amongst all ZBTB proteins, could not be resolved, probably owing to its flexibility. Molecular-dynamics simulations suggest a contribution of this loop to modulation of the mammalian BTB dimerization interface. ISSN 2059-7983 research papers 582 Piepoli et al. PATZ1 BTB domain homodimer Acta Cryst. (2020). D76, 581-593Figure 1Sequence alignment of BTB domains of ZBTB transcription factors identifies a unique central region in PATZ1 that is conserved in mammals. (a) Sequence alignment of PATZ1 BTB domains from selected vertebrate species. The unique central sequence of the A2/B3 loop that is conserved in mammals and is missing in fish and amphibians is indicated in bold. (b) Sequence alignment of selected human ZBTB proteins and their predicted secondary structure. The sequences of the human PATZ1 and cKrox BTB domains with their unique extra region between the A2 helix and B3 strand are shown above. The PATZ1 amino acids that correspond to this region without electron-density assignments from the crystal structure are shown in bold. Arrows and rods identify predicted conserved -strand and -helical regions. The eight BTB domains with solved structures are annotated on the left with their common names in addition to the ZBTB nomenclature. Shading, asterisks, colons and periods identify conserved residues according to the Clustal format. A consensus sequence is shown at the bottom, with the three predicted degron residues involved in BTB domain stability indicated by arrows. research papers Acta Cryst. (2020). D76, 581-593 Piepoli et al. PATZ1 BTB domain homodimer 583 research papers Acta Cryst. (2020). D76, 581-593 Piepoli et al. PATZ1 BTB domain homodimer 591

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“…6 To our knowledge, only 15 cases of non-brain EWSR1-PATZ1 fusion sarcomas have been reported (Table II). 2,[7][8][9] No previous report has detailed the presentation, imaging, and treatment course of an EWSR1-PATZ1 sarcoma of the head and neck.…”

Section: Discussionmentioning

confidence: 99%

“…7 Only two prior cases of this variant have been reported in the head and neck since 2000, but in brief as part of a case series. 2,[7][8][9] Thus, we provide a detailed report of the presentation, workup, and management of a new case of ESWR1-PATZ1 sarcoma of soft tissue neck origin.…”

Section: Introductionmentioning

confidence: 99%

Round Cell Sarcoma with EWSR1‐PATZ1 Gene Fusion in the Neck: Case Report and Review of the Literature

et al. 2020

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EWSR1-PATZ1 is a rare gene fusion recently recognized to occur in round and spindle cell sarcomas. To date, fewer than 20 cases have been described in the literature. However, no dedicated case reports have detailed its presentation in the head and neck region. We recently cared for a 52-year-old woman with an isolated, single right level 5A cervical mass. Excisional biopsy at an external hospital revealed pathology results consistent with EWSR1-PATZ1 polyphenotypic round and spindle cell sarcoma. The patient subsequently underwent surgical excision of the tumor and right neck lymph node dissection followed by adjuvant chemoradiation.

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Spindle and Round Cell Sarcoma With EWSR1-PATZ1 Gene Fusion

Cited by 65 publications

References 33 publications

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

Structural analysis of the PATZ1 BTB domain homodimer

Round Cell Sarcoma with EWSR1‐PATZ1 Gene Fusion in the Neck: Case Report and Review of the Literature

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