EWSRI-CREBI is the predominant gene fusion in angiomatoid fibrous histiocytoma Journal Article
| Authors: | Antonescu, C. R.; Cin, P. D.; Nafa, K.; Teot, L. A.; Surti, U.; Fletcher, C. D.; Ladanyi, M. |
| Article Title: | EWSRI-CREBI is the predominant gene fusion in angiomatoid fibrous histiocytoma |
| Abstract: | The molecular hallmark of angiomatoid fibrous histiocytoma (AFH) is not well defined, with only six cases with specific gene fusions reported to date, consisting of either FUS-ATF1 or EWSR1-ATF1. To address this, we investigated the presence of FUS-ATF1, EWSR1-ATF1, and the highly related EWSR1-CREB1 fusion in a group of nine AFHs. All cases were subjected to RT-PCR for EWSR1-ATF1 and EWSR1-CREB1. FISH for EWSR1 and FUS rearrangements was performed in most cases. Transcriptional profiling was performed in three tumors and their gene expression was compared to five clear cell sarcomas expressing either the EWSR1-ATF1 or EWSR1-CREB1 fusion. By RT-PCR, eight out of nine tumors showed the presence of the EWSR1-CREB1 fusion, while one had an EWSR1-ATF1 transcript. FISH showed evidence of EWSR1 rearrangement in seven out of eight cases. Karyotypic analysis performed in one tumor showed a t(2;22)(q33;q12). High transcript levels were noted for TFE3 in AFH tumors, while overexpression of genes involved in melanogenesis, such as MITF, GP100, and MET was noted in somatic clear cell sarcomas. We report for the first time the presence of EWSR1-CREB1 in AFH, which now appears to be the most frequent gene fusion in this tumor. EWSR1-CREB1 is a novel translocation recently described in clear cell sarcoma of the GI tract. EWSR1-ATF1, identified in some AFH cases, is the most common genetic abnormality in soft tissue clear cell sarcoma. Thus, identical fusions involving ATF1 and CREB1 are found in two distinct sarcomas, which may be able to transform two different types of mesenchymal precursor cells, unlike most other sarcoma gene fusions. © 2007 Wiley-Liss, Inc. |
| Keywords: | adolescent; adult; child; clinical article; human tissue; preschool child; aged; child, preschool; middle aged; unclassified drug; gene translocation; human cell; genetics; metabolism; in situ hybridization, fluorescence; gene overexpression; reverse transcription polymerase chain reaction; gene expression; genetic transcription; pathology; rna binding protein; rna-binding proteins; fluorescence in situ hybridization; gene rearrangement; reverse transcriptase polymerase chain reaction; gene fusion; soft tissue sarcoma; chromosome translocation; mesenchymal stem cell; dermatofibroma; malignant fibrous histiocytoma; gastrointestinal tract; malignant transformation; chromosome analysis; karyotype; calmodulin binding protein; ewsr1 protein, human; calmodulin-binding proteins; cytogenetic analysis; melanogenesis; clear cell sarcoma; cyclic amp responsive element binding protein; cyclic amp response element-binding protein; tfe3 gene; histiocytoma, malignant fibrous; angiomatoid fibrous histiocytoma; afh gene; atfi gene; crebi gene; ewsri aatfi gene; ewsri crebi gene; fus atfi gene; gp100 gene; met gene; mitf gene; creb1 protein, human |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 46 |
| Issue: | 12 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2007-12-01 |
| Start Page: | 1051 |
| End Page: | 1060 |
| Language: | English |
| DOI: | 10.1002/gcc.20491 |
| PUBMED: | 17724745 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 42" - "Export Date: 17 November 2011" - "CODEN: GCCAE" - "Source: Scopus" |
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