Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion: Report of 3 Cases
Language English Country United States Media print
Document type Case Reports, Journal Article
- MeSH
- Adenocarcinoma, Clear Cell genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Cyclic AMP Response Element Modulator genetics MeSH
- Tongue Neoplasms genetics pathology MeSH
- Nasopharyngeal Neoplasms genetics MeSH
- Lung Neoplasms genetics pathology MeSH
- Oncogene Fusion MeSH
- RNA-Binding Protein EWS genetics MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Transcriptome MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- CREM protein, human MeSH Browser
- EWSR1 protein, human MeSH Browser
- Cyclic AMP Response Element Modulator MeSH
- RNA-Binding Protein EWS MeSH
We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in the base of tongue, lung, and nasopharynx were studied. All cases shared a clear cell morphology with hyalinized stroma, presence of mucin and p63 positivity and were initially diagnosed as mucoepidermoid carcinoma but were negative for evidence of any of the expected gene fusions. Anchored multiplex polymerase chain reaction demonstrated a EWSR1-CREM fusion in all 3 cases to confirm a diagnosis of CCC. This finding is biologically justified as CREM and ATF1 both belong to the CREB family of transcription factors. EWSR1-CREM fusions have not been previously reported in CCC and have only rarely been reported in other tumors. We show that the ability to discover novel gene variants with next-generation sequencing-based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.
Anatomic Pathology St Paul's Hospital Vancouver BC Canada
Czech Republic Bioptic Laboratory Ltd Molecular Pathology Laboratory Plzen Czechia
Czech Republic Medicyt Ltd Kosice Slovak Republic
Department of Anatomical Pathology Vancouver General Hospital
Department of Pathology and Laboratory Medicine University of British Columbia
Department of Pathology Beaumont Hospital and the Royal College of Surgeons Dublin Ireland
Department of Pathology Faculty of Medicine in Plzen Charles University
References provided by Crossref.org
Molecular pathology in diagnosis and prognostication of head and neck tumors
