@article{OroujiPeitschOroujietal.2020,
  author    = {Orouji, Elias and Peitsch, Wiebke K. and Orouji, Azadeh and Houben, Roland and Utikal, Jochen},
  title     = {Unique role of histone methyltransferase PRDM8 in the tumorigenesis of virus-negative Merkel cell carcinoma},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {4},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12041057},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203815},
  year      = {2020},
  abstract  = {Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80\% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.},
  language  = {en}
}
@article{BehrPeitschHametneretal.2014,
  author    = {Behr, Daniel S. and Peitsch, Wiebke K. and Hametner, Christian and Lasitschka, Felix and Houben, Roland and Sch{\"o}nhaar, Kathrin and Michel, Julia and Dollt, Claudia and Goebeler, Matthias and Marx, Alexander and Goerdt, Sergij and Schmieder, Astrid},
  title     = {Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas},
  series = {International Journal of Clinical and Experimental Pathology},
  volume    = {7},
  journal   = {International Journal of Clinical and Experimental Pathology},
  number    = {11},
  issn      = {1936-2625},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117720},
  pages     = {7610-7621},
  year      = {2014},
  abstract  = {Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival.},
  language  = {en}
}
@article{OroujiPeitschOroujietal.2020,
  author    = {Orouji, Elias and Peitsch, Wiebke K. and Orouji, Azadeh and Houben, Roland and Utikal, Jochen},
  title     = {Oncogenic role of an epigenetic reader of m\(^6\)A RNA modification: YTHDF1 in Merkel cell carcinoma},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {1},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12010202},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200815},
  year      = {2020},
  abstract  = {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 N\(^6\)-methyladenosine (m\(^6\)A) RNA modifications, to have high copy gains and to be highly expressed in Merkel cell carcinoma. Importantly, we identified the presence of m\(^6\)A 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 YTHDF1\(^{high}\) MCC patients compared to YTHDF1\(^{low}\) patients. Our findings indicate a novel oncogenic role of YTHDF1 through m\(^6\)A machinery in the tumorigenesis of MCC.},
  language  = {en}
}