High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas Journal Article
| Authors: | Italiano, A.; Sung, Y. S.; Zhang, L.; Singer, S.; Maki, R. G.; Coindre, J. M.; Antonescu, C. R. |
| Article Title: | High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas |
| 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. © 2011 Wiley Periodicals, Inc. |
| Keywords: | immunohistochemistry; adolescent; adult; clinical article; human tissue; aged; middle aged; unclassified drug; in situ hybridization, fluorescence; reverse transcription polymerase chain reaction; antineoplastic combined chemotherapy protocols; tumor markers, biological; transcription factor; cyclophosphamide; vincristine; homeodomain proteins; ewing sarcoma; sarcoma; molecular cloning; fluorescence in situ hybridization; gene rearrangement; molecular sequence data; messenger rna; screening; oncogene proteins, fusion; dactinomycin; base sequence; translocation, genetic; dna sequence; cancer classification; repressor proteins; genomic dna; soft tissue neoplasms; complementary dna; chromosome 4q; chromosome 10q; oncogene fusion; rna-binding protein fus; chromosomes, human, pair 4; homeobox; sarcoma, small cell; transcription factor dux4; primitive round cell sarcoma; small blue round cell sarcoma; small blue round cell tumor; chromosomes, human, pair 10 |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 51 |
| Issue: | 3 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2012-03-01 |
| Start Page: | 207 |
| End Page: | 218 |
| Language: | English |
| DOI: | 10.1002/gcc.20945 |
| PROVIDER: | scopus |
| PUBMED: | 22072439 |
| PMCID: | PMC3404826 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: GCCAE" - "Source: Scopus" |
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