EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma

Covinsky, Michael; Gong, Steven; Rajaram, Veena; Perry, Arie; Pfeifer, John D.

doi:10.1016/j.humpath.2004.10.015

Cited by 73 publications

(64 citation statements)

References 48 publications

(54 reference statements)

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“…It is difficult to distinguish CCS from primary or metastatic melanoma based on morphology, immunohistochemical profile, and even with ultrastructural features. Covinsky et al (24) emphasized the use of molecular genetic testing for accurate diagnosis of CCS, which harbors EWS-ATF1 fusion transcript and the associated t(12;22)(q13;q12) translocation, in contrast to cutaneous melanoma. This possibility could not be excluded because of the lack of fresh tissue and available molecular testing.…”

Section: Discussionmentioning

confidence: 99%

Colonic malignant melanoma, primary or metastatic? Case report

Serın

Doğanavşargıl²,

Çalışkan³

et al. 2010

Turk J Gastroenterol

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Section: Discussionmentioning

confidence: 99%

Colonic malignant melanoma, primary or metastatic? Case report

Serın

Doğanavşargıl²,

Çalışkan³

et al. 2010

Turk J Gastroenterol

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“…However, 6 of 7 cases of conventional CCS of the gastrointestinal tract were found to contain melanin where there was an active search for pigmentation. [20][21][22][23] Most CCSLGTs show extensive areas of tumor necrosis and often show high mitotic activity. 13 …”

Section: Pathologic Features Of Ccslgt Morphologymentioning

confidence: 99%

Clear Cell Sarcoma–like Tumor of the Gastrointestinal Tract: An Evolving Entity

Wang

Thway

2015

Archives of Pathology &Amp; Laboratory Medicine

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Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm that occurs in the wall of the small bowel, stomach, or large bowel, predominantly in young adults. It is an aggressive neoplasm that frequently presents with metastatic disease and has a high mortality rate. Histologically, it is usually composed of medium-sized primitive ovoid or epithelioid cells with pale or clear cytoplasm that are arranged in sheets or in papillary or alveolar architectures. Clear cell sarcoma-like tumor of the gastrointestinal tract is positive for S100 protein, invariably negative for melanocytespecific markers and is often also positive for neuroendocrine markers. The etiology of CCSLGT is unknown, but many studies have shown associations with EWSR1-CREB1 gene fusions and, less frequently, with EWSR1-ATF1 fusions. Here, we discuss the current status of CCSLGT, including histologic, immunophenotypic, and molecular findings.

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“…Indeed, most CCS share a melanocytic gene expression signature with melanomas (1). However, CCS are also genetically distinct from melanomas, as they lack BRAF mutations (2) and show, in most cases, a recurrent chromosomal translocation t(12;22)(q13;q12), resulting in the fusion of the EWS gene (also known as EWSR1) on 22q12 with the activating transcription factor-1 gene (ATF1) on 12q13 (3 -6).Primary CCSs of the gastrointestinal tract are rare (7,8). Gastrointestinal CCS includes a histologic variant rich in osteoclast-type giant cells which uniformly express S100 protein, but lack melanocytic differentiation by immunohistochemistry, being negative for HMB45 and Mart-1 (9).…”

mentioning

confidence: 99%

“…Primary CCSs of the gastrointestinal tract are rare (7,8). Gastrointestinal CCS includes a histologic variant rich in osteoclast-type giant cells which uniformly express S100 protein, but lack melanocytic differentiation by immunohistochemistry, being negative for HMB45 and Mart-1 (9).…”

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confidence: 99%

EWS-CREB1: A Recurrent Variant Fusion in Clear Cell Sarcoma—Association with Gastrointestinal Location and Absence of Melanocytic Differentiation

Antonescu

Nafa²,

Segal³

et al. 2006

Clinical Cancer Research

296

267

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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.Clear cell sarcoma (CCS), also known as melanoma of soft parts, typically presents in the deep soft tissues of the lower extremity, in close proximity to tendons, fascia, or aponeuroses. Young adults are preferentially affected and the clinical course is often marked by regional and distant metastases. Most CCS show immunoreactivity for melanoma markers, such as HMB45, and contain melanosomes. Indeed, most CCS share a melanocytic gene expression signature with melanomas (1). However, CCS are also genetically distinct from melanomas, as they lack BRAF mutations (2) and show, in most cases, a recurrent chromosomal translocation t(12;22)(q13;q12), resulting in the fusion of the EWS gene (also known as EWSR1) on 22q12 with the activating transcription factor-1 gene (ATF1) on 12q13 (3 -6).Primary CCSs of the gastrointestinal tract are rare (7,8). Gastrointestinal CCS includes a histologic variant rich in osteoclast-type giant cells which uniformly express S100 protein, but lack melanocytic differentiation by immunohistochemistry, being negative for HMB45 and Mart-1 (9). As a result of its rarity in the gastrointestinal tract, the differential diagnosis of CCS in this site includes more common mesenchymal or neuroectodermal neoplasms,...

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EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma

Cited by 73 publications

References 48 publications

Colonic malignant melanoma, primary or metastatic? Case report

Colonic malignant melanoma, primary or metastatic? Case report

Clear Cell Sarcoma–like Tumor of the Gastrointestinal Tract: An Evolving Entity

EWS-CREB1: A Recurrent Variant Fusion in Clear Cell Sarcoma—Association with Gastrointestinal Location and Absence of Melanocytic Differentiation

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