Abstract P203: Milademetan is a potent, murine double minute 2 (MDM2) inhibitor, highly active in TP53 wild-type (p53WT) Merkel cell carcinoma (MCC) cell lines

2021 ◽  
Author(s):  
Varsha Ananthapadmanabhan ◽  
Aine Knott ◽  
Kara M. Soroko ◽  
Prafulla C. Gokhale ◽  
Vijaya Tirunagaru ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Wild Type ◽  
Highly Active ◽  
Double Minute ◽  
Murine Double Minute ◽  
Mdm2 Inhibitor

scholarly journals 098 Co-expression of epidermal keratins and neuroendocrine markers in Merkel cell carcinoma tumors and cell lines

2016 ◽  
Vol 136 (5) ◽  
pp. S18
Author(s):  
D. Mangelberger ◽  
M.E. Verhaegen ◽  
P.W. Harms ◽  
A. Durham ◽  
J.H. Kozlow ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Neuroendocrine Markers

Characterisation of four merkel cell carcinoma adherent cell lines

1995 ◽  
Vol 60 (1) ◽  
pp. 100-107 ◽  
Author(s):  
J. Helen Leonard ◽  
Peter Dash ◽  
Peter Holland ◽  
John H. Kearsley ◽  
John R. Bell
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Adherent Cell ◽  
Merkel Cell

Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive Merkel cell carcinoma cell lines

PROTEOMICS ◽  
2016 ◽  
Vol 16 (19) ◽  
pp. 2587-2591 ◽  
Author(s):  
Aelita Konstantinell ◽  
Jack-Ansgar Bruun ◽  
Randi Olsen ◽  
Augusta Aspar ◽  
Nataša Škalko-Basnet ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Merkel Cell Carcinoma ◽  
Carcinoma Cell ◽  
Merkel Cell ◽  
Carcinoma Cell Lines

scholarly journals DNA-methylation patterns imply a common cellular origin of virus- and UV-associated Merkel cell carcinoma

Oncogene ◽  
2021 ◽  
Author(s):  
Jan Gravemeyer ◽  
Ivelina Spassova ◽  
Monique E. Verhaegen ◽  
Andrzej A. Dlugosz ◽  
Daniel Hoffmann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Marker Genes ◽  
Methylation Data ◽  
Merkel Cell ◽  
Scoring Model ◽  
Methylation Patterns ◽  
Neuroendocrine Cancers

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.

scholarly journals MiR-375 Regulation of LDHB Plays Distinct Roles in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 443 ◽  
Author(s):  
Satendra Kumar ◽  
Hong Xie ◽  
Patrick Scicluna ◽  
Linkiat Lee ◽  
Viveca Björnhagen ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Normal Skin ◽  
Ectopic Expression ◽  
Growth Effect ◽  
Merkel Cell ◽  
Multiple Tumor ◽  
Induced Apoptosis

MicroRNA-375 (miR-375) is deregulated in multiple tumor types and regulates important targets involved in tumorigenesis and metastasis. This miRNA is highly expressed in Merkel cell carcinoma (MCC) compared to normal skin and other non-MCC skin cancers, and its expression is high in Merkel cell polyomavirus (MCPyV)-positive (MCPyV+) and low in MCPyV-negative (MCPyV−) MCC tumors. In this study, we characterized the function and target of miR-375 in MCPyV+ and MCPyV− MCC cell lines. Ectopic expression of miR-375 in MCPyV− MCC cells resulted in decreased cell proliferation and migration, as well as increased cell apoptosis and cell cycle arrest. However, in MCPyV+ MCC cells, inhibition of miR-375 expression reduced cell growth and induced apoptosis. Additionally, the expression of lactate dehydrogenase B (LDHB), a known target of miR-375, was inversely correlated with miR-375. Silencing of LDHB reduced cell growth in MCPyV− cell lines, while its silencing in MCPyV+ cell lines rescued the cell growth effect mediated by miR-375 inhibition. Together, our results suggest dual roles of miR-375 and LDHB in MCPyV and non-MCPyV-associated MCCs. We propose that LDHB could be a therapeutic target in MCC and different strategies should be applied in virus- and non-virus-associated MCCs.

scholarly journals Comparison of Mutant and Wild-Type p53 Proteins in Merkel Cell Carcinoma

2000 ◽  
Vol 7 (2) ◽  
pp. 326-326 ◽  
Author(s):  
Henry J. Carson ◽  
Nathan E. Lueck ◽  
Bruce C. Horten
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Wild Type ◽  
Wild Type P53

scholarly journals Mutational Landscape of Virus- and UV-Associated Merkel Cell Carcinoma Cell Lines Is Comparable to Tumor Tissue

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 649
Author(s):  
Kai Horny ◽  
Patricia Gerhardt ◽  
Angela Hebel-Cherouny ◽  
Corinna Wülbeck ◽  
Jochen Utikal ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Growth Pattern ◽  
Uv Light ◽  
Copy Number Variations ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Functional Studies ◽  
Negative Cell

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. However, the genomic characteristics of MCC cell lines used as preclinical models are not well established. Thus, we analyzed the exomes of three virus-negative and six virus-positive MCC cell lines, all showing a classical neuroendocrine growth pattern. Virus-negative cell lines are characterized by a high tumor mutational burden (TMB), UV-light-induced DNA damage, functionally relevant coding mutations, e.g., in RB1 and TP53, and large amounts of copy number variations (CNVs). In contrast, virus-positive cell lines have a low TMB with few coding mutations and lack prominent mutational signatures, but harbor characteristic CNVs. One of the virus-negative cell lines has a local MYC amplification associated with high MYC mRNA expression. In conclusion, virus-positive and -negative MCC cell lines with a neuroendocrine growth pattern resemble mutational features observed in MCC tissue samples, which strengthens their utility for functional studies.

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