APOBEC3A expression in penile squamous cell carcinoma
Background: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hyperm...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
Pathobiology
Year: 2018, Volume: 85, Issue: 3, Pages: 169-178 |
| ISSN: | 1423-0291 |
| DOI: | 10.1159/000479007 |
| Online Access: | Verlag, kostenfrei registrierungspflichtig, Volltext: http://dx.doi.org/10.1159/000479007 Verlag, kostenfrei registrierungspflichtig, Volltext: https://www.karger.com/Article/FullText/479007 
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| Author Notes: | Martina Heller, Elena-Sophie Prigge, Adam Kaczorowski, Magnus von Knebel Doeberitz, Markus Hohenfellner, Stefan Duensing |
| Summary: | Background: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hypermutation signature has been discovered in cervical cancer, which is intimately associated with infection by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes themselves are subject to DNA editing by APOBECs. Similar to cervical cancer, a proportion of penile squamous cell carcinomas (SCCs) is etiologically driven by high-risk HPVs, but very little is known about the role of APOBECs in penile SCC development and progression. Methods: A series of 34 penile SCCs was analyzed for the expression of APOBEC3A protein by immunohistochemistry. HPV genotyping was carried out using a bead-based multiplex hybridization assay preceded by BSGP5+6+ primer-based amplification. Results: We found a frequent reduction of APOBEC3A protein expression in the invasive parts of the majority of HPV-negative penile SCCs. In contrast, the majority of HPV-positive penile SCCs retained APOBEC3A expression during malignant progression. Conclusion: Our results suggest that APOBEC3A expression is downregulated during progression towards invasiveness in HPV-negative penile SCC, but maintained in HPV-positive penile SCC. How high-risk HPV-infected tumor cells tolerate high APOBEC3A, which appears to exert tumor suppressive functions in HPV-negative penile SCCs, remains to be elucidated. |
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| Item Description: | Gesehen am 23.04.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1423-0291 |
| DOI: | 10.1159/000479007 |