EWS-CREB1: A recurrent variant fusion in clear cell sarcoma - Association with gastrointestinal location and absence of melanocytic differentiation Journal Article
| Authors: | Antonescu, C. R.; Nafa, K.; Segal, N. H.; Dal Cin, P.; Ladanyi, M. |
| Article Title: | EWS-CREB1: A recurrent variant fusion in clear cell sarcoma - Association with gastrointestinal location and absence of melanocytic differentiation |
| Abstract: | Purpose: Clear cell sarcoma (CCS) usually arises in the lower extremities of young adults and is typically associated with a t(12;22) translocation resulting in the fusion of EWS (EWSR1) with ATF1, a gene encoding a member of the cyclic AMP - responsive element binding protein (CREB) family of transcription factors. CCS arising in the gastrointestinal tract is rare and its pathologic and molecular features are not well defined. Experimental Design: We report a novel variant fusion of EWS to CREB1, a gene at 2q32 encoding another CREB family member highly related to ATF1, detected in three women with gastrointestinal CCS. All three cases contained an identical EWS-CREB1 fusion transcript that was shown by reverse transcription-PCR. In two of the cases tested, EWS gene rearrangement was also confirmed by fluorescence in situ hybridization and the EWS-CREB1 genomic junction fragments were isolated by long-range DNA PCR. Results: Morphologically, all three tumors lacked melanin pigmentation. By immunohistochemistry, there was a strong and diffuse S100 protein reactivity, whereas all melanocytic markers were negative. Ultrastructurally, two of the cases lacked melanosomes. The melanocyte-specific transcript of MITF was absent in two cases, and only weakly expressed in the third case. The Affymetrix gene expression data available in one case showed lower expression of the melanocytic genes MITF, TYR, and TYRP1, compared with four EWS-ATF1-positive CCSs of non-gastrointestinal origin. Conclusions: EWS-CREB1 may define a novel subset of CCS that occurs preferentially in the gastrointestinal tract and shows little or no melanocytic differentiation. Thus, evidence of melanocytic lineage or differentiation is not a necessary feature of sarcomas with gene fusions involving CREB family members. © 2006 American Association for Cancer Research. |
| Keywords: | immunohistochemistry; adult; human tissue; aged; aged, 80 and over; human cell; dna-binding proteins; case report; fluorouracil; electron microscopy; reverse transcription polymerase chain reaction; melanin; melanocyte; melanocytes; tumor differentiation; genetic association; genetic variability; cell differentiation; transcription factors; nuclear proteins; gastrointestinal neoplasms; fluorescence in situ hybridization; gene rearrangement; molecular sequence data; hybrid protein; reverse transcriptase polymerase chain reaction; microarray analysis; folinic acid; oncogene proteins, fusion; base sequence; protein s 100; chromosome aberrations; sequence homology, nucleic acid; microphthalmia associated transcription factor; rna binding protein ews; gene location; clear cell sarcoma; sarcoma, clear cell; cyclic amp responsive element binding protein; cyclic amp response element-binding protein; dna fragment; rna-binding protein ews; chromosome 2q; activating transcription factor 1; melanosome |
| Journal Title: | Clinical Cancer Research |
| Volume: | 12 |
| Issue: | 18 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2006-09-15 |
| Start Page: | 5356 |
| End Page: | 5362 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-05-2811 |
| PUBMED: | 17000668 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 72" - "Export Date: 4 June 2012" - "CODEN: CCREF" - "Source: Scopus" |
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