Clear Cell Odontogenic Carcinoma: First Report of Novel EWSR1–CREM Fusion Gene in Case of Long-Term Misdiagnosis

Breik, Omar; Higginson, James; Al-Ajami, Abdulla K.; Mohamed, Abubakar; Martin, Tim; Amel‐Kashipaz, R.

doi:10.1007/s12105-021-01302-y

Cited by 18 publications

(27 citation statements)

References 33 publications

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“…Our results, which are consistent with those of other investigators, show that CCOC appears to be driven by translocations that produce fusions between EWSR1 and CREB family transcription factors, including ATF1 and CREM. To our knowledge, this is the second report of intraosseous CCOC with an EWSR1-CREM translocation-the first being reported by Breik et al 1 in February 2021. These fusions (EWSR1-ATF1 and EWSR1-CREM) are also detected in CCC.…”

Section: Discussionmentioning

confidence: 60%

Section: Statement Of Clinical Relevancementioning

confidence: 99%

“…To date, several studies 1,[11][12][13][14][15][16] have described the genetics of CCOC. Seventeen CCOC specimens have been tested for Ewing sarcoma breakpoint region 1 (EWSR1) translocations using either fluorescence in situ hybridization (FISH) 1,[14][15][16] or real-time polymerase chain reaction (RT-PCR) and FISH analysis. 12 Genetic analysis showed that EWSR1 was partnered with cyclic AMP-dependent transcription factor (ATF1) in 7 samples, cAMP response element-binding protein (CREB) in 1 sample, and recently, cAMP responsive element modulator (CREM) in 1 sample.…”

Section: Statement Of Clinical Relevancementioning

confidence: 99%

“…12 Genetic analysis showed that EWSR1 was partnered with cyclic AMP-dependent transcription factor (ATF1) in 7 samples, cAMP response element-binding protein (CREB) in 1 sample, and recently, cAMP responsive element modulator (CREM) in 1 sample. 1 The remainder of the samples had an unknown rearrangement location and/ or partner. Five specimens were negative for an EWSR1 translocation.…”

Section: Statement Of Clinical Relevancementioning

confidence: 99%

“…Targeted RNA-seq is a method for the detection of fusion transcripts that has been shown to have robust performance in paraffin-embedded samples, broad coverage of common fusions, and the ability to detect novel fusion partners. [1][2][3][4] Clear cell odontogenic carcinoma (CCOC) is a rare jaw tumor, with 107 cases documented between 1985 to 2019 worldwide. 5 The tumor was first described in 1985 by Hansen et al 6 as a benign odontogenic tumor with a tendency for local recurrence.…”

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confidence: 99%

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Detection of EWSR1 fusions in CCOC by targeted RNA-seq

Rivera

Faquin

Thierauf

et al. 2022

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Section: Discussionmentioning

confidence: 60%

Section: Statement Of Clinical Relevancementioning

confidence: 99%

Section: Statement Of Clinical Relevancementioning

confidence: 99%

Section: Statement Of Clinical Relevancementioning

confidence: 99%

mentioning

confidence: 99%

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Detection of EWSR1 fusions in CCOC by targeted RNA-seq

Rivera

Faquin

Thierauf

et al. 2022

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

Javaid

Patton

Tinoco

et al. 2022

Genes Chromosomes & Cancer

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Chromosomal translocations with gene fusions are uniquely rare events in paraganglioma, mostly involving UBTF::MAML3 gene fusion. Precedent literature suggests that tumors involving MAML3 gene fusion correlate with poor clinical outcomes. Herein, we report a case of metastatic sporadic paraganglioma harboring EWSR1::CREM gene fusion in a 36‐year‐old male, that has not been previously described. The patient presented with large paraspinal mass that was resected the same year. Tumor recurred 3‐years later and on further work‐up, patient was found to have metastases involving both lungs. Histopathologic evaluation of the original primary tumor showed tightly packed irregular nests and cords of cells containing palely eosinophilic cytoplasm. Features considered atypical included: areas of solid growth pattern, coagulative tumor necrosis, focal cellular atypia and angiolymphatic invasion were also identified. By immunohistochemistry, the tumor cells were positive for synaptophysin and chromogranin and negative for keratin. The S100 stain highlights the sustentacular cells and the Ki‐67 proliferation index of 15%. The recurrence specimen was similar but showed increased cellularity, atypia, necrosis, and proliferative activity (Ki‐67 proliferation index of 35%). CT guided biopsy of the right lung lesion was consistent with metastasis. Next generation sequencing identified EWSR1::CREM fusion. The breakpoints were found in chromosome 22: 29683123 for EWSR1 exon 7 (NM_005243.3) and at chromosome 10:35495823 for CREM exon 6 (NM_001267562.1). Fluorescence in situ hybridization for EWSR1 gene rearrangement was positive. In summary, we report a case of metastatic paraganglioma with EWSR1::CREM gene fusion, not previously described in this entity, and expands on the phenotypic diversity within the genetic landscape of EWSR1::CREM gene fusion positive tumors.

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A novel SMARCA2‐CREM fusion expending the molecular spectrum of salivary gland hyalinazing clear cell carcinoma beyond the FET genes

Lanic

Guerin²,

Sater

et al. 2022

Genes Chromosomes & Cancer

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Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland carcinoma with a generally indolent behavior, characterized by recurrent chromosomal translocation involving EWSR1 (22q12.2) leading to two fusion genes EWSR1::ATF1 or EWSR1::CREM. We report one case of HCCC with a novel SMARCA2::CREM fusion, identified by targeted RNA next generation sequencing by LD-RT-PCR, which has until now never been described in salivary glands. The exon 4 of SMARCA2 is fused to exon 5 of CREM. This fusion has been described previously in only one tumor, a central nervous system tumor (intracranial mesenchymal tumor) but not in other FET::CREB fused tumors. This fusion was confirmed by CREM break-apart FISH and reverse transcriptase polymerase chain reaction (RT-PCR). The tumor cells showed retained expression of INI1, SMARCA2, and SMARCA4 by immunohistochemistry. We compare its clinical, histopathological, immunophenotypic, genetic features with those previously described in HCCC, FET::CREB fusion-positive. Our results added data suggesting that different histomolecular tumor subtypes seem to be included within the terminology "HCCC, FET:: CREB fusion-positive," and that further series of cases are needed to better characterize them.

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Clear Cell Odontogenic Carcinoma: First Report of Novel EWSR1–CREM Fusion Gene in Case of Long-Term Misdiagnosis

Cited by 18 publications

References 33 publications

Detection of EWSR1 fusions in CCOC by targeted RNA-seq

Detection of EWSR1 fusions in CCOC by targeted RNA-seq

Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

A novel SMARCA2‐CREM fusion expending the molecular spectrum of salivary gland hyalinazing clear cell carcinoma beyond the FET genes

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