High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas
Antoine Italiano,Yun Shao Sung,Lei Zhang,Samuel Singer,Robert G. Maki,Jean-Michel Coindre,Cristina R. Antonescu +6 more
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TLDR
The results suggest the possibility of a newly defined subgroup of primitive round cell sarcomas characterized by CIC rearrangements, distinct from Ewing sarcoma family of tumors.Abstract:
Primitive round cell sarcomas of childhood and young adults have been problematic to diagnose and classify. Our goal was to investigate the pathologic and molecular characteristics of small blue round cell tumors (SBRCT) that remained unclassified after exhaustive immunohistochemistry and molecular screening to exclude known sarcoma-related translocations. As rare examples of EWSR1-negative SBRCT have been shown to carry rearrangements for FUS and CIC genes, we undertook a systematic screening for these two genes. CIC rearrangements by FISH were detected in 15/22 (68%), while none showed FUS abnormalities. RACE, RT-PCR, and/or long-range DNA PCR performed in two cases with frozen material showed that CIC was fused to copies of the DUX4 gene on either 4q35 or 10q26.3. Subsequent FISH analysis confirmed fused signals of CIC with either 4q35 or 10q26.3 region in six cases each. Tumors positive for CIC-DUX4 fusion occurred mainly in male young adult patients (median age: 29 years), with the extremities being the most frequent location. Microscopically, tumors displayed a primitive, round to oval cell morphology with prominent nucleoli, high mitotic count, and areas of necrosis. O13 expression was variable, being either diffuse or patchy and tumors mostly lacked other markers of differentiation. Although CIC-DUX4 resulting in a t(4;19) translocation has been previously described in primitive sarcomas, this is the first report implicating the related DUX4 on 10q26 in oncogenesis. These results suggest the possibility of a newly defined subgroup of primitive round cell sarcomas characterized by CIC rearrangements, distinct from Ewing sarcoma family of tumors.read more
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The evolving classification of soft tissue tumours – an update based on the new 2013 WHO classification
TL;DR: A brief overview summarizes changes in the classification in each of the broad categories of soft tissue tumour (adipocytic, fibroblastic, etc.) and also provides a short summary of newer genetic data which have been incorporated in the WHO classification.
Journal ArticleDOI
WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition.
TL;DR: The fourth edition of the World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone was published in February 2013, and serves to provide an updated classification scheme and reproducible diagnostic criteria for pathologists.
Journal ArticleDOI
Sarcoma classification: an update based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone.
TL;DR: Changes in the classification of soft tissue and bone sarcomas as well as tumors of intermediate biologic potential in the 2013 World Health Organization volume are reviewed, new molecular insights into these tumors, and associated surgical and clinical implications are reviewed.
Journal ArticleDOI
The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation
Andrew S. Brohl,David A. Solomon,Wendy Chang,Jianjun Wang,Young K. Song,Sivasish Sindiri,Rajesh Patidar,Laura Hurd,Li Chen,Jack F. Shern,Hongling Liao,Xinyu Wen,Julia Gerard,Jung-Sik Kim,Jose Antonio Lopez Guerrero,Isidro Machado,Daniel H. Wai,Piero Picci,Timothy J. Triche,Andrew E. Horvai,Markku Miettinen,Jun S. Wei,Daniel Catchpool,Antonio Llombart-Bosch,Todd Waldman,Javed Khan +25 more
TL;DR: The largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines) is reported, finding that EFT has a very low mutational burden but frequent deleterious mutations in the cohesin complex subunit STAG2 and that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and these tumors do not have a characteristic Ewing sarcoma gene expression signature.
Journal ArticleDOI
Refinements in Sarcoma Classification in the Current 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone
Vickie Y. Jo,Leona A. Doyle +1 more
TL;DR: The fourth edition of the World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone was published in February 2013 and provides an updated classification scheme and reproducible diagnostic criteria, based on recent clinicopathologic studies and genetic and molecular data.
References
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Journal Article
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In-Sang Jeon,J. N. Davis,Benjamin S. Braun,J. E. Sublett,Martine F. Roussel,Christopher T. Denny,David N. Shapiro +6 more
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TL;DR: It is found that a subset of soft tissue ME tumors with clear cell morphology harbor an EWSR1‐POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases, and these findings do not support a pathogenetic relationship between soft tissue Me tumors and their salivary gland counterparts.