title: Hotspot mutations in polyomavirus positive and negative Merkel cell carcinomas.
abstract: Merkel cell polyomavirus (MCV) infection underlies most Merkel cell carcinoma (MCC), a primary neuroendocrine carcinoma of the skin. While previous research has focused on MCV-positive MCC tumors, less is known about the oncogenesis in MCV-negative tumors. In this study, we analyzed mutational status of 27 MCC tumors with known MCV status for hotspot regions of 50 cancer-related genes by targeted next-generation sequencing using the Ion AmpliSeq Cancer Hotspot Panel. In addition to previously reported TP53, KIT, and PIK3CA gene mutations, we found somatic mutations in the tyrosine kinase domain of the EGFR gene in a small proportion of the cells in six tumor tissues. RB1 mutations were seen only in virus negative tumors. Hotspot mutations were more frequent in MCV-negative tumors, although the difference was not statistically significant. No clear hotspot mutation profile was observed. Novel RB1 mutations were detected only in MCV-negative tumors.
authors.affiliation: Department of Pathology, University of Helsinki, Helsinki, Finland.
authors.forename: Tuukka
authors.initials: T
authors.lastname: Veija
authors.affiliation: Department of Pathology, University of Helsinki, Helsinki, Finland.
authors.forename: Virinder Kaur
authors.initials: VK
authors.lastname: Sarhadi
authors.affiliation: Plastic Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Virve
authors.initials: V
authors.lastname: Koljonen
authors.affiliation: Department of Pathology, University of Helsinki, Helsinki, Finland.
authors.forename: Tom
authors.initials: T
authors.lastname: Bohling
authors.affiliation: Department of Pathology, University of Helsinki, Helsinki, Finland. Electronic address: sakari.knuutila@helsinki.fi.
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000235:genetics* / Q000821:virology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D059965:Merkel cell polyomavirus / Q000302:isolation & purification*; D008875:Middle Aged; D009154:Mutation; D027601:Polyomavirus Infections / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000821:virology*; D014412:Tumor Virus Infections / Q000235:genetics* / Q000473:pathology
keywords: Merkel cell carcinoma; mutations; next-generation sequencing