title: Merkel cell polyomavirus and HPV-17 associated with cutaneous squamous cell carcinoma arising in a patient with melanoma treated with the BRAF inhibitor dabrafenib.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Division of Cancer Medicine, Departmentof Investigational Cancer Therapeutics, Phase I Clinical Trials Program, MD Anderson Cancer Center, Houston, TX 77030, USA. gfalchoo@mdanderson.org
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Peter
authors.initials: P
authors.lastname: Rady
authors.forename: Sharon
authors.initials: S
authors.lastname: Hymes
authors.forename: Harrison P
authors.initials: HP
authors.lastname: Nguyen
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015266:Carcinoma, Merkel Cell / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D059965:Merkel cell polyomavirus / Q000302:isolation & purification; D008875:Middle Aged; D010091:Oximes / Q000009:adverse effects / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000150:complications / Q000473:pathology / Q000821:virology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology*
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D007093:Imidazoles; D010091:Oximes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
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