EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location
Yu Chien Kao,Yun Shao Sung,Lei Zhang,Chun-Liang Chen,Sumathi Vaiyapuri,Marc K. Rosenblum,Cristina R. Antonescu +6 more
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TLDR
A distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations is reported, suggesting a novel entity.Abstract:
Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.read more
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NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and Visceral Tumors.
Brendan C. Dickson,Yun-Shao Sung,Marc K. Rosenblum,Victor E. Reuter,Mohammed Harb,Jay S. Wunder,David Swanson,Cristina R. Antonescu +7 more
TL;DR: It is established that NUT-associated tumors transgress the midline and account for a subset of primitive neoplasms occurring in soft tissue and viscera.
Journal ArticleDOI
Gastroblastoma harbors a recurrent somatic MALAT1 – GLI1 fusion gene
Rondell P. Graham,Asha Nair,Jaime I. Davila,Long Jin,Jin Jen,William R. Sukov,Tsung Teh Wu,Henry D. Appelman,Jorge Torres-Mora,Kyle D. Perry,Lizhi Zhang,Sara M. Kloft-Nelson,Ryan A. Knudson,Patricia T. Greipp,Andrew L. Folpe +14 more
TL;DR: An oncogenic MALAT1–GLI1 fusion gene is identified in all cases of gastroblastoma that may serve as a diagnostic biomarker.
Journal ArticleDOI
What turns CREB on? And off? And why does it matter?
André Steven,Michael Friedrich,Paul Jank,Nadine Heimer,Jan Budczies,Carsten Denkert,Barbara Seliger +6 more
TL;DR: The clinical relevance of CREB is summarized, including its use as a prognostic and/or predictive marker as well as a therapeutic target.
Journal ArticleDOI
Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion: Report of 3 Cases.
Erin Chapman,Alena Skálová,Nikola Ptáková,Petr Martinek,Angela Goytain,Tracy Tucker,Wei Xiong,Mary Leader,Brian Kudlow,Josh Haimes,Malcolm Hayes,Peter Bohus,Marketa Miesbauerova,Cheng-Han Lee,Tony Ng,Tony Ng +15 more
TL;DR: It is shown that the ability to discover novel gene variants with next-generation sequencing–based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.
Journal ArticleDOI
A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.
Patrice Desmeules,Philippe Joubert,Lei Zhang,Hikmat Al-Ahmadie,Christopher D.M. Fletcher,Efsevia Vakiani,Deborah DeLair,Natasha Rekhtman,Marc Ladanyi,William D. Travis,Cristina R. Antonescu +10 more
TL;DR: The spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions is expanded to include a subgroup of conventional epithelioid MM, and features of this unique MM subset include young age at presentation, lack of asbestos exposure and retained BAP1 expression.
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