Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schrama, D; Groesser, L; Ugurel, S; Hafner, C; Pastrana, DV; Buck, CB; Cerroni, L; Theiler, A; Becker, JC.
Presence of human polyomavirus 6 in mutation-specific BRAF inhibitor-induced epithelial proliferations.
JAMA Dermatol. 2014; 150(11):1180-1186
Doi: 10.1001/jamadermatol.2014.1116
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Schrama David
- Co-Autor*innen der Med Uni Graz
- Cerroni Lorenzo
- Theiler Anna
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- A frequent adverse effect of mutation-specific BRAF inhibitor therapy is the induction of epithelial proliferations including cutaneous squamous cell carcinomas. To date, the only factor identified contributing to their development is the activation of the mitogen-activated signal transduction cascade by mutations in the RAS genes. However, these mutations explain only 60% of the tumors; hence, it is important to identify what is causing the remaining tumors. To test for the presence of human papillomaviruses (HPVs) and the recently identified human polyomaviruses (HPyVs), Merkel cell polyomavirus (MCPyV), and trichodysplasia spinulosa-associated polyomavirus (TSPyV), as well as HPyV-6, HPyV-7, HPyV-9, and HPyV-10, in epithelial proliferations occurring after BRAF inhibitor therapy to determine whether these oncogenic viruses may contribute to BRAF inhibitor-induced skin tumors. Retrospective study at a university hospital in Austria of epithelial proliferations that developed in patients with melanoma after initiation of treatment with the BRAF inhibitor vemurafenib. Samples were analyzed for (1) presence of the most frequently observed RAS mutations by SNaPshot technology, (2) detection of the viruses by real-time polymerase chain reaction, and (3) presence of capsid proteins of the most abundantly detected virus by immunohistochemical analysis. RAS mutational status, as well as HPV and HPyV presence, in BRAF inhibitor-induced epithelial proliferations. Eighteen biopsy samples from 6 patients were retrieved from our hospital's archive. We identified RAS mutations in 10 (62%) of the 16 samples with clear results. DNA of HPyV-9, HPyV-10, and TSPyV were virtually absent in the samples. MCPyV DNA was present in 13 of 18 samples, and HPV, HPyV-6, and HPyV-7 DNA were present in all samples. In general, the amount of DNA encoding the latter viruses was rather low, with the exception of HPyV-6 in several samples of 1 individual patient. Notably, the relevance of the presence of HPyV-6 in the epithelial proliferation was underlined by immunohistochemical detection of the core protein VP1 of HPyV-6. The presence of both high HPyV-6 DNA load and VP1 protein suggests that polyomaviruses may contribute to the epithelial proliferations observed in patients receiving BRAF inhibitor therapy, albeit the relative impact as compared with that of RAS mutations appears circumstantial.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Antineoplastic Agents - adverse effects
- Antineoplastic Agents - therapeutic use
- Biopsy -
- Carcinoma, Squamous Cell - epidemiology
- Carcinoma, Squamous Cell - virology
- DNA, Viral - isolation & purification
- Female -
- Genes, ras - genetics
- Humans -
- Indoles - adverse effects
- Indoles - therapeutic use
- Melanoma - drug therapy
- Melanoma - pathology
- Middle Aged -
- Mutation -
- Papillomaviridae - isolation & purification
- Papillomavirus Infections - pathology
- Papillomavirus Infections - virology
- Polyomavirus - isolation & purification
- Polyomavirus Infections - epidemiology
- Polyomavirus Infections - pathology
- Polyomavirus Infections - virology
- Proto-Oncogene Proteins B-raf - antagonists & inhibitors
- Real-Time Polymerase Chain Reaction -
- Retrospective Studies -
- Skin Neoplasms - drug therapy
- Skin Neoplasms - epidemiology
- Skin Neoplasms - virology
- Sulfonamides - adverse effects
- Sulfonamides - therapeutic use
- Tumor Virus Infections - epidemiology
- Tumor Virus Infections - pathology
- Tumor Virus Infections - virology
- Vemurafenib -