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Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or durin...

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Zeitschriftentitel: International Journal of Cancer
Personen und Körperschaften: Schrama, David, Sarosi, Eva‐Maria, Adam, Christian, Ritter, Cathrin, Kaemmerer, Ulrike, Klopocki, Eva, König, Eva‐Maria, Utikal, Jochen, Becker, Jürgen C., Houben, Roland
In: International Journal of Cancer, 145, 2019, 4, S. 1020-1032
Medientyp: E-Article
Sprache: Englisch
veröffentlicht:
Wiley
Schlagwörter:
author_facet Schrama, David
Sarosi, Eva‐Maria
Adam, Christian
Ritter, Cathrin
Kaemmerer, Ulrike
Klopocki, Eva
König, Eva‐Maria
Utikal, Jochen
Becker, Jürgen C.
Houben, Roland
Schrama, David
Sarosi, Eva‐Maria
Adam, Christian
Ritter, Cathrin
Kaemmerer, Ulrike
Klopocki, Eva
König, Eva‐Maria
Utikal, Jochen
Becker, Jürgen C.
Houben, Roland
author Schrama, David
Sarosi, Eva‐Maria
Adam, Christian
Ritter, Cathrin
Kaemmerer, Ulrike
Klopocki, Eva
König, Eva‐Maria
Utikal, Jochen
Becker, Jürgen C.
Houben, Roland
spellingShingle Schrama, David
Sarosi, Eva‐Maria
Adam, Christian
Ritter, Cathrin
Kaemmerer, Ulrike
Klopocki, Eva
König, Eva‐Maria
Utikal, Jochen
Becker, Jürgen C.
Houben, Roland
International Journal of Cancer
Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
Cancer Research
Oncology
author_sort schrama, david
spelling Schrama, David Sarosi, Eva‐Maria Adam, Christian Ritter, Cathrin Kaemmerer, Ulrike Klopocki, Eva König, Eva‐Maria Utikal, Jochen Becker, Jürgen C. Houben, Roland 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.32280 <jats:p>Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus‐induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV‐positive MCC cell lines. Microarray‐based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin‐20 and neuron‐specific enolase as well as truncated MCPyV‐encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV‐integration sites in introns of different genes. The LT‐truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT‐truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV‐positive MCC cell lines, which are likely to serve as valuable tools in future MCC research.</jats:p> Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration International Journal of Cancer
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title Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_unstemmed Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_full Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_fullStr Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_full_unstemmed Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_short Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_sort characterization of six merkel cell polyomavirus‐positive merkel cell carcinoma cell lines: integration pattern suggest that large t antigen truncating events occur before or during integration
topic Cancer Research
Oncology
url http://dx.doi.org/10.1002/ijc.32280
publishDate 2019
physical 1020-1032
description <jats:p>Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus‐induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV‐positive MCC cell lines. Microarray‐based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin‐20 and neuron‐specific enolase as well as truncated MCPyV‐encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV‐integration sites in introns of different genes. The LT‐truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT‐truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV‐positive MCC cell lines, which are likely to serve as valuable tools in future MCC research.</jats:p>
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author Schrama, David, Sarosi, Eva‐Maria, Adam, Christian, Ritter, Cathrin, Kaemmerer, Ulrike, Klopocki, Eva, König, Eva‐Maria, Utikal, Jochen, Becker, Jürgen C., Houben, Roland
author_facet Schrama, David, Sarosi, Eva‐Maria, Adam, Christian, Ritter, Cathrin, Kaemmerer, Ulrike, Klopocki, Eva, König, Eva‐Maria, Utikal, Jochen, Becker, Jürgen C., Houben, Roland, Schrama, David, Sarosi, Eva‐Maria, Adam, Christian, Ritter, Cathrin, Kaemmerer, Ulrike, Klopocki, Eva, König, Eva‐Maria, Utikal, Jochen, Becker, Jürgen C., Houben, Roland
author_sort schrama, david
container_issue 4
container_start_page 1020
container_title International Journal of Cancer
container_volume 145
description <jats:p>Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus‐induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV‐positive MCC cell lines. Microarray‐based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin‐20 and neuron‐specific enolase as well as truncated MCPyV‐encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV‐integration sites in introns of different genes. The LT‐truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT‐truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV‐positive MCC cell lines, which are likely to serve as valuable tools in future MCC research.</jats:p>
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spelling Schrama, David Sarosi, Eva‐Maria Adam, Christian Ritter, Cathrin Kaemmerer, Ulrike Klopocki, Eva König, Eva‐Maria Utikal, Jochen Becker, Jürgen C. Houben, Roland 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.32280 <jats:p>Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus‐induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV‐positive MCC cell lines. Microarray‐based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin‐20 and neuron‐specific enolase as well as truncated MCPyV‐encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV‐integration sites in introns of different genes. The LT‐truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT‐truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV‐positive MCC cell lines, which are likely to serve as valuable tools in future MCC research.</jats:p> Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration International Journal of Cancer
spellingShingle Schrama, David, Sarosi, Eva‐Maria, Adam, Christian, Ritter, Cathrin, Kaemmerer, Ulrike, Klopocki, Eva, König, Eva‐Maria, Utikal, Jochen, Becker, Jürgen C., Houben, Roland, International Journal of Cancer, Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration, Cancer Research, Oncology
title Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_full Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_fullStr Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_full_unstemmed Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_short Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
title_sort characterization of six merkel cell polyomavirus‐positive merkel cell carcinoma cell lines: integration pattern suggest that large t antigen truncating events occur before or during integration
title_unstemmed Characterization of six Merkel cell polyomavirus‐positive Merkel cell carcinoma cell lines: Integration pattern suggest that large T antigen truncating events occur before or during integration
topic Cancer Research, Oncology
url http://dx.doi.org/10.1002/ijc.32280