Faculty Collaboration Database

Merkel cell polyomavirus and HPV-17 associated with cutaneous squamous cell carcinoma arising in a patient with melanoma treated with the BRAF inhibitor dabrafenib. JAMA Dermatol 2013 Mar;149(3):322-6

Date

04/05/2013

Pubmed ID

23552670

Pubmed Central ID

PMC4085990

DOI

10.1001/jamadermatol.2013.2023

Scopus ID

2-s2.0-84875399925 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

IMPORTANCE: Approximately 10% to 25% of patients treated with BRAF inhibitors develop cutaneous squamous cell carcinoma (SCC), but the mechanism responsible has not yet been determined. We report what we believe to be the first case in which Merkel cell polyomavirus (MCPyV) and human papillomavirus subtype 17 (HPV-17) were associated with cutaneous SCC that developed during treatment with the BRAF inhibitor dabrafenib.

OBSERVATIONS: A 62-year-old woman with V600E BRAF -mutant metastatic melanoma enrolled in a phase 1 trial of dabrafenib, a selective inhibitor of V600-mutant BRAF kinase. During the first 6 weeks of treatment, the patient developed multiple skin lesions, including a 6-mm crusted papule on the left eyebrow, which was resected and, on pathology examination, revealed SCC. The DNA extracted from paraffin-embedded tissue was amplified by polymerase chain reaction for detection of MCPyV and epidermodysplasia verruciformis HPV (EV-HPV) types. Analysis of the cloned and sequenced polymerase chain reaction products revealed the presence of MCPyV and HPV-17 DNA. Other EV-HPV subtypes were not detected.

CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report demonstrating the coexistence of MCPyV and HPV-17 in cutaneous SCC. Because both viruses have oncogenic potential, their role in the development of BRAF inhibitor-related SCC merits further investigation.

Author List

Falchook GS, Rady P, Hymes S, Nguyen HP, Tyring SK, Prieto VG, Hong DS, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Carcinoma, Merkel Cell
Carcinoma, Squamous Cell
DNA, Viral
Female
Humans
Imidazoles
Melanoma
Merkel cell polyomavirus
Middle Aged
Oximes
Papillomavirus Infections
Polymerase Chain Reaction
Polyomavirus Infections
Proto-Oncogene Proteins B-raf
Skin Neoplasms
Tumor Virus Infections