The diversity of soft tissue tumours with <i><scp>EWSR</scp>1</i> gene rearrangements: a review

Fisher, Cyril

doi:10.1111/his.12269

Cited by 150 publications

(131 citation statements)

References 207 publications

(368 reference statements)

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“…28 However, heterozygous EWSR1 loss, resulting in a low level of the EWSR1 protein itself, may also contribute to the development of cancers, and this has not been explored fully. Here we report that EWSR1 plays an important role in mitotic progression independent of its nuclear role.…”

Section: Discussionmentioning

confidence: 99%

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

et al. 2016

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EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with a-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycledependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

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Section: Discussionmentioning

confidence: 99%

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

et al. 2016

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“…18 While FUS-ATF1 fusions have so far not been detected in other neoplasms, EWSR1-CREB1 and EWSR1-ATF1 fusions are not unique to AFH and have been consistently described in a number of different tumor groups that are clinically and usually histopathologically distinct from AFH. 57 The significant diversity of soft tissue neoplasms associated with EWSR1 gene rearrangements is well known 58 ; EWSR1 is capable of fusing with several different partner genes, which can sometimes result in the formation of histologically identical neoplasms but can also fuse with the same genes to generate morphologically and behaviorally different tumors. It is not fully understood how identical gene fusions can generate such different tumor types, although a possible explanation might be that these neoplasms originate from specific progenitor cells in different anatomic sites, 59 with the differing phenotypes corresponding to the particular cell of origin.…”

Section: Histopathologymentioning

confidence: 99%

“…Myxoid stroma is described in some lung AFH but as a focal finding without the prominence seen in PPMS. 58 Myoepithelial tumors of soft tissue often also have a reticular pattern, demonstrate considerable immunophenotypical heterogeneity, and occur in age groups (between the second and fourth decades, with about one-fifth occurring in children) and sites (most frequently in extremities, limb girdles, and then head and neck and trunk) similar to those of AFH. Histologically, myoepithelial tumors show a wide morphologic spectrum but may demonstrate ductular or tubular differentiation or chondromyxoid-type stroma, which is never seen in AFH.…”

Section: Differential Diagnosismentioning

confidence: 99%

Angiomatoid Fibrous Histiocytoma: The Current Status of Pathology and Genetics

Thway

Fisher

2015

Archives of Pathology &Amp; Laboratory Medicine

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117

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Context.-Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the superficial extremities of children and young adults. While it has characteristic histologic features of nodular distributions of ovoid and spindle cells with blood-filled cystic cavities and a surrounding dense lymphoplasmacytic infiltrate, there is a significant morphologic spectrum, which coupled with its rarity and lack of specific immunoprofile can make diagnosis challenging. Angiomatoid fibrous histiocytoma is associated with 3 characteristic gene fusions, EWSR1-CREB1 and EWSR1-ATF1, which are also described in other neoplasms, and rarely FUS-ATF1. Angiomatoid fibrous histiocytoma is now recognized at an increasing number of sites and is known to display a variety of unusual histologic features.Objective.-To review the current status of AFH, discussing putative etiology, histopathology with variant morphology and differential diagnosis, and current genetics, including overlap with other tumors harboring EWSR1-CREB1 and EWSR1-ATF1 fusions.Data Sources.-Review of published literature, including case series, case reports, and review articles, in online medical databases.Conclusions.-The occurrence of AFH at several unusual anatomic sites and its spectrum of morphologic patterns can result in significant diagnostic difficulty, and correct diagnosis is particularly important because of its small risk of metastasis and death. This highlights the importance of diagnostic recognition, ancillary molecular genetic confirmation, and close clinical follow-up of patients with AFH. Further insight into the genetic and epigenetic changes arising secondary to the characteristic gene fusions of AFH will be integral to understanding its tumorigenic mechanisms.

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“…There are few clinical data regarding this sarcoma type, but reported metastatic sites include the liver, lymph nodes and other intra-abdominal sites (2). This entity was first described in 2003 by Zambrano et al (3), who described six cases of a biologically-aggressive neoplasm affecting sites exclusively within the gastrointestinal tract which showed similarities to soft tissue clear cell sarcoma (CCS), also referred to as clear cell sarcoma of soft parts or conventional-type clear cell sarcoma, which typically affects extremity deep soft tissue sites, particularly around the foot and ankle (4,5).…”

Section: Abstract Background/aim: Clear Cell Sarcoma-like Tumor Of Tmentioning

confidence: 99%

“…EWSR1 rearrangements have been described in many clinically and histologically different sarcomas, including desmoplastic small round cell tumor, Ewing sarcoma, extraskeletal myxoid chondrosarcoma, myxoid liposarcoma, angiomatoid fibrous histiocytoma and primary pulmonary myxoid sarcoma (4)(5)(6). The most frequent translocation in soft tissue CCS is t(12:22)(q13;q12) resulting in the fusion of EWSR1 and ATF1 genes (7), while another translocation t(2;22)(q32.3;q12), results in EWSR1-CREB1 fusion.…”

Section: Abstract Background/aim: Clear Cell Sarcoma-like Tumor Of Tmentioning

confidence: 99%