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.

scholarly journals Merkel Cell Polyomavirus-Infected Merkel Cell Carcinoma Cells Require Expression of Viral T Antigens

2010 ◽  
Vol 84 (14) ◽  
pp. 7064-7072 ◽  
Author(s):  
Roland Houben ◽  
Masahiro Shuda ◽  
Rita Weinkam ◽  
David Schrama ◽  
Huichen Feng ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Annexin V ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
T Antigens ◽  
Negative Cell ◽  
Exon 1

ABSTRACT Merkel cell carcinoma (MCC) is the most aggressive skin cancer. Recently, it was demonstrated that human Merkel cell polyomavirus (MCV) is clonally integrated in ∼80% of MCC tumors. However, direct evidence for whether oncogenic viral proteins are needed for the maintenance of MCC cells is still missing. To address this question, we knocked down MCV T-antigen (TA) expression in MCV-positive MCC cell lines using three different short hairpin RNA (shRNA)-expressing vectors targeting exon 1 of the TAs. The MCC cell lines used include three newly generated MCV-infected cell lines and one MCV-negative cell line from MCC tumors. Notably, all MCV-positive MCC cell lines underwent growth arrest and/or cell death upon TA knockdown, whereas the proliferation of MCV-negative cell lines remained unaffected. Despite an increase in the number of annexin V-positive, 7-amino-actinomycin D (7-AAD)-negative cells upon TA knockdown, activation of caspases or changes in the expression and phosphorylation of Bcl-2 family members were not consistently detected after TA suppression. Our study provides the first direct experimental evidence that TA expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC.

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

scholarly journals Characterization of the Merkel Cell Carcinoma miRNome

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Matthew S. Ning ◽  
Annette S. Kim ◽  
Nripesh Prasad ◽  
Shawn E. Levy ◽  
Huiqiu Zhang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Normal Skin ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Skin Cancers ◽  
Next Generation Sequencing Ngs

MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis.In situhybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research.

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

scholarly journals Features Predicting Sentinel Lymph Node Positivity in Merkel Cell Carcinoma

2011 ◽  
Vol 29 (8) ◽  
pp. 1036-1041 ◽  
Author(s):  
Jennifer L. Schwartz ◽  
Kent A. Griffith ◽  
Lori Lowe ◽  
Sandra L. Wong ◽  
Scott A. McLean ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Growth Pattern ◽  
Regional Lymph Node ◽  
Mitotic Rate ◽  
Tumor Thickness ◽  
Merkel Cell ◽  
Primary Tumors

Purpose Merkel cell carcinoma (MCC) is a relatively rare, potentially aggressive cutaneous malignancy. We examined the clinical and histologic features of primary MCC that may correlate with the probability of a positive sentinel lymph node (SLN). Methods Ninety-five patients with MCC who underwent SLN biopsy at the University of Michigan were identified. SLN biopsy was performed on 97 primary tumors, and an SLN was identified in 93 instances. These were reviewed for clinical and histologic features and associated SLN positivity. Univariate associations between these characteristics and a positive SLN were tested for by using either the χ2 or the Fisher's exact test. A backward elimination algorithm was used to help create a best multiple variable model to explain a positive SLN. Results SLN positivity was significantly associated with the clinical size of the lesion, greatest horizontal histologic dimension, tumor thickness, mitotic rate, and histologic growth pattern. Two competing multivariate models were generated to predict a positive SLN. The histologic growth pattern was present in both models and combined with either tumor thickness or mitotic rate. Conclusion Increasing clinical size, increasing tumor thickness, increasing mitotic rate, and infiltrative tumor growth pattern were significantly associated with a greater likelihood of a positive SLN. By using the growth pattern and tumor thickness model, no subgroup of patients was predicted to have a lower than 15% to 20% likelihood of a positive SLN. This suggests that all patients presenting with MCC without clinical evidence of regional lymph node disease should be considered for SLN biopsy.

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.

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