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Mutational landscape of virus- and UV-associated Merkel cell carcinoma cell lines is comparable to tumor tissue

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. How...

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Main Authors: Horny, Kai (Author) , Gerhardt, Patricia (Author) , Hebel-Cherouny, Angela (Author) , Wülbeck, Corinna (Author) , Utikal, Jochen (Author) , Becker, Jürgen C. (Author)
Format: Article (Journal)
Language:English
Published: 5 February 2021
In: Cancers
Year: 2021, Volume: 13, Issue: 4, Pages: 1-15
ISSN:2072-6694
DOI:10.3390/cancers13040649
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13040649
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/4/649
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Author Notes:Kai Horny, Patricia Gerhardt, Angela Hebel-Cherouny, Corinna Wülbeck, Jochen Utikal and Jürgen C. Becker
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Summary: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.
Item Description:Gesehen am 08.09.2021
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers13040649

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