Supplementary Material for: 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 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.