scholarly journals Oncogenic Role of an Epigenetic Reader of m6A RNA Modification: YTHDF1 in Merkel Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 202 ◽  
Author(s):  
Orouji ◽  
Peitsch ◽  
Orouji ◽  
Houben ◽  
Utikal
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Survival Data ◽  
T Antigen ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Rna Modification ◽  
Merkel Cell ◽  
Small T Antigen

Merkel cell carcinoma is a deadly skin cancer, which in the majority of cases is caused by the Merkel cell polyomavirus (MCPyV). The viral small T antigen is regarded as the dominant oncoprotein expressed in the tumor cells. We used genomic screening of copy number aberrations along with transcriptomic analysis to investigate regions with amplification that harbor differentially expressed genes. We identified YTHDF1, a protein that is a reader of N6-methyladenosine (m6A) RNA modifications, to have high copy gains and to be highly expressed in Merkel cell carcinoma. Importantly, we identified the presence of m6A on small T antigen mRNA suggesting a relation between YTHDF1 amplification and MCPyV gene expression. Interestingly, knockdown of YTHDF1 in Merkel cell carcinoma (MCC) cell lines negatively affected the translation initiation factor eIF3 and reduced proliferation and clonogenic capacity in vitro. Furthermore, analysis of survival data revealed worse overall survival in YTHDF1high MCC patients compared to YTHDF1low patients. Our findings indicate a novel oncogenic role of YTHDF1 through m6A machinery in the tumorigenesis of MCC.

scholarly journals Merkel Cell Polyomavirus–Positive Merkel Cell Carcinoma Cells Do Not Require Expression of the Viral Small T Antigen

2013 ◽  
Vol 133 (8) ◽  
pp. 2059-2064 ◽  
Author(s):  
Sabrina Angermeyer ◽  
Sonja Hesbacher ◽  
Jürgen C. Becker ◽  
David Schrama ◽  
Roland Houben
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Carcinoma Cells ◽  
Merkel Cell ◽  
Small T Antigen

scholarly journals Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice

2017 ◽  
Vol 77 (12) ◽  
pp. 3151-3157 ◽  
Author(s):  
Monique E. Verhaegen ◽  
Doris Mangelberger ◽  
Paul W. Harms ◽  
Markus Eberl ◽  
Dawn M. Wilbert ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Tumor Development ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Small T Antigen

scholarly journals 134 Functional role of merkel cell polyomavirus T-antigen regulated microRNAs in merkel cell carcinoma

2018 ◽  
Vol 138 (5) ◽  
pp. S23
Author(s):  
S. Kumar ◽  
H. Xie ◽  
H. Shi ◽  
L. Lee ◽  
V. Björnhagen ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Functional Role ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell

The essential role of radiation therapy in securing locoregional control of merkel cell carcinoma

1990 ◽  
Vol 19 (3) ◽  
pp. 583-591 ◽  
Author(s):  
William H. Morrison ◽  
Lester J. Peters ◽  
Elvio G. Silva ◽  
Charles D. Wendt ◽  
K.Kian Ang ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Essential Role ◽  
Locoregional Control ◽  
Merkel Cell

scholarly journals Immunotherapy in Merkel cell carcinoma: role of Avelumab

2018 ◽  
Vol Volume 7 ◽  
pp. 15-19 ◽  
Author(s):  
Amruth Palla ◽  
Donald Doll
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell

scholarly journals Merkel Cell Carcinoma: Recent Progress and Current Priorities on Etiology, Pathogenesis, and Clinical Management

2009 ◽  
Vol 27 (24) ◽  
pp. 4021-4026 ◽  
Author(s):  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Clinical Management ◽  
Expression Profiles ◽  
T Antigen ◽  
Neuroendocrine Cells ◽  
Human Polyomavirus ◽  
Adjuvant Radiation ◽  
Cytokeratin 20 ◽  
Merkel Cell

Purpose To expedite improved understanding, diagnosis, treatment, and prevention of Merkel cell carcinoma (MCC), a rare malignancy of cutaneous neuroendocrine cells that has a 28% 2-year mortality rate. Methods This article summarizes a workshop that discussed the state-of-the-art research and priorities for research on MCC and on a new human polyomavirus (ie, MCPyV) recently discovered in 80% of MCC tumors. Results Normal Merkel cells are widely distributed in the epidermis near the end of nerve axons and may function as mechanoreceptors or chemoreceptors. Malignant MCC cells typically stain for cytokeratin 20 as well as for other epithelial and neuroendocrine markers. MCC subtypes, which are based on histology, on cell line growth properties, and on gene expression profiles, have been reported but have not been linked to prognosis. Clinical management has been empiric. MCPyV is clonally integrated at various sites in the human genome of MCC tumors, with truncating mutations in the viral, large T antigen gene that interrupt viral replication. MCPyV seroprevalence may be high, as with previously known human polyomaviruses. MCC risk is increased 11-fold with AIDS and with other cell-mediated immune deficiencies, B-cell neoplasms, and ultraviolet radiation exposure. Conclusion Development and validation of a range quantitative polymerase chain reaction and serologic assays for detection of MCPyV, as well as an infectious clone of the virus, would clarify the fundamental biology, natural history, and epidemiology of the virus, of MCC, and of other diseases. Contingent on standardized histologic diagnosis and staging of MCC, consortia are needed to clarify the risks and benefits of sentinel lymph node biopsy, adjuvant radiation therapy, and salvage therapies; consortia are needed also for epidemiologic studies of MCC etiology.

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