Expression of Transcription Factor CREM in Human Tissues

Abstract

Cyclic AMP element modulator (CREM) is a transcription factor best known for its intricate involvement in spermatogenesis. The CREM gene encodes for multiple protein isoforms, which can enhance or repress transcription of target genes. Recent studies have identified fusion genes, with CREM as a partner gene in many neoplastic diseases. EWSR1-CREM fusion genes have been found in several mesenchymal tumors and in salivary gland carcinoma. These genes encode fusion proteins that include the C-terminal DNA-binding domain of CREM. We used a transcriptomic approach and immunohistochemistry to study the expression of CREM isoforms that include DNA-binding domains across human tissues. We found that CREM protein is widely expressed in almost all normal human tissues. A transcriptomic analysis of normal tissues and cancer showed that transcription of CREM can be altered in tumors, suggesting that also wild-type CREM may be involved in cancer biology. The wide expression of CREM protein in normal human tissues and cancer may limit the utility of immunohistochemistry for identification of tumors with CREM fusions:

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

“…CREM (cyclic AMP response element modulator) is widely expressed in human tissue and regulates the expression of other genes. 25 The SMARCA2 gene, located at 9p24.3, belongs to the SWI/SNF chromatin remodeling complex. SMARCA2 mutations are present in carcinomas and concomitant loss of SMARCA4 and SMARCA2 expressions in sarcomas.…”

“…CREM (cyclic AMP response element modulator) is widely expressed in human tissue and regulates the expression of other genes 25 …”

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

“…This possibility is sustained by the change in gene expression profiling in EVs. Indeed, not only are EV-naive no more enriched in DUSP6 [ 30 ], but EV-RIPC rearrange their gene content and become enriched in some stress- and cell-cycle-related genes [ 53 , 54 , 55 , 56 , 57 ]. We can speculate that DUSP6 enrichment in the hearts treated with EV-RIPC may represent a challenge to counteract the increase in Erk-1/2 activation.…”

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

“…8 Cyclic AMP element modulator (CREM), a member of the CREB family of transcription factors, is a transcription factor that is expressed widely in human tissue and regulates the expression of other genes. 9 The EWS RNA binding protein 1 (EWSR1) regulate a variety of cellular processes including gene expression and RNA processing. EWSR1 gene rearrangements are frequently seen in a growing number of epithelial and soft tissue tumors.…”

“…10 On the other hand, CREM gene rearrangements are relatively novel and infrequent, compared to other members of the CREB transcription factors (inclusive of ATF1 and CREB1), and occur commonly in partnership with EWSR1. 9,11 They have been reported in a variety of unrelated phenotypical diverse epithelial and mesenchymal tumors with differing prognosis including: hyalinizing clear cell tumors of oral cavity and oropharynx, myxoid mesenchymal tumors, angiomatoid fibrous histiocytoma, abdominal epithelioid neoplasm, spindle/small cell carcinoma, clear cell odontogenic neoplasm, and pulmonary mesenchymal neoplasm [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Herein, we report for the first time, a unique case of a metastatic sporadic paraganglioma harboring a unique EWSR1::CREM gene fusion, in a 36 year old male. To the best of our knowledge, this is the first case of metastatic paraganglioma harboring the EWSR1::CREM gene fusion.…”