TY  - JOUR
AU  - Heller, Martina
AU  - Prigge, Elena-Sophie
AU  - Kaczorowski, Adam
AU  - von Knebel Doeberitz, Magnus
AU  - Hohenfellner, Markus
AU  - Duensing, Stefan
TI  - APOBEC3A Expression in Penile Squamous Cell Carcinoma.
JO  - Pathobiology
VL  - 85
IS  - 3
SN  - 1423-0291
CY  - Basel
PB  - Karger
M1  - DKFZ-2018-00642
SP  - 169 - 178
PY  - 2018
AB  - 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.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.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.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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29166639
DO  - DOI:10.1159/000479007
UR  - https://inrepo02.dkfz.de/record/134852
ER  -