Merkel Cell Carcinoma
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Oncogene ◽  
2021 ◽  
Author(s):  
Jan Gravemeyer ◽  
Ivelina Spassova ◽  
Monique E. Verhaegen ◽  
Andrzej A. Dlugosz ◽  
Daniel Hoffmann ◽  
...  

AbstractMerkel cell carcinoma (MCC) is a neuroendocrine tumor either induced by integration of the Merkel cell polyomavirus into the cell genome or by accumulation of UV-light-associated mutations (VP-MCC and UV-MCC). Whether VP- and UV-MCC have the same or different cellular origins is unclear; with mesenchymal or epidermal origins discussed. DNA-methylation patterns have a proven utility in determining cellular origins of cancers. Therefore, we used this approach to uncover evidence regarding the cell of origin of classical VP- and UV-MCC cell lines, i.e., cell lines with a neuroendocrine growth pattern (n = 9 and n = 4, respectively). Surprisingly, we observed high global similarities in the DNA-methylation of UV- and VP-MCC cell lines. CpGs of lower methylation in VP-MCC cell lines were associated with neuroendocrine marker genes such as SOX2 and INSM1, or linked to binding sites of EZH2 and SUZ12 of the polycomb repressive complex 2, i.e., genes with an impact on carcinogenesis and differentiation of neuroendocrine cancers. Thus, the observed differences appear to be rooted in viral compared to mutation-driven carcinogenesis rather than distinct cells of origin. To test this hypothesis, we used principal component analysis, to compare DNA-methylation data from different epithelial and non-epithelial neuroendocrine cancers and established a scoring model for epithelial and neuroendocrine characteristics. Subsequently, we applied this scoring model to the DNA-methylation data of the VP- and UV-MCC cell lines, revealing that both clearly scored as epithelial cancers. In summary, our comprehensive analysis of DNA-methylation suggests a common epithelial origin of UV- and VP-MCC cell lines.


Author(s):  
Akira Yoshida ◽  
Satoshi Kuwamoto ◽  
Hiroki Kurumi ◽  
Hajime Isomoto

Author(s):  
Kristan Schiele ◽  
Priscilla Ly Kojder ◽  
Alex B Haynes ◽  
Anthony Soldano ◽  
Anokhi Jambusaria‐Pahlajani

2021 ◽  
pp. jnumed.121.262882
Author(s):  
Sonia Mahajan ◽  
Christopher A. Barker ◽  
Audrey Mauguen ◽  
Sandra P. D'Angelo ◽  
Randy Yeh ◽  
...  

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dan Xu ◽  
Sheng Jiang ◽  
Yue He ◽  
Xiang Jin ◽  
Gan Zhao ◽  
...  

AbstractMerkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a high mortality rate, while Merkel cell polyomavirus (MCV) has been pointed as the causative agent of MCC. A better prognosis of MCC associated with a high level of antibodies against the capsid protein VP1 suggests that anti-VP1 immune response might be essential against MCC growth. In the current study, we developed a VP1-target vaccine formulated with CRA. Using a tumorigenic CMS5-VP1 tumor model, the vaccine-induced a potent antitumor efficacy in a dose-dependent manner was evidently demonstrated and mainly mediated by both VP1-specific CD4+ and CD8+ T-cell responses against the growth of CMS5-VP1 tumors in vaccinated BALB/c mice since the depletion of CD4+ and CD8+ T cells reverse the antitumor effects. Thus, immunotherapy with this vaccine represents a novel approach for the clinical treatment of aggressive MCV-related MCC in humans.


2021 ◽  
Vol Volume 14 ◽  
pp. 711-717
Author(s):  
Branislav Bystricky ◽  
Filip Kohutek ◽  
Zuzana Miklatkova ◽  
Tomas Sedlacek ◽  
Viliam Gal ◽  
...  

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