title: Aberrant expression of ALK and EZH2 in Merkel cell carcinoma.
abstract: Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC.
  
  
  
  RNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite™ Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue.
  
  
  
  ALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors.
  
  
  
  High expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, FI-00014, Helsinki, Finland. tuukka.veija@helsinki.fi.
authors.forename: Tuukka
authors.initials: T
authors.lastname: Veija
authors.affiliation: Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Topeliuksenkatu 5, P.O. Box 266, FI-00029, Helsinki, Finland.
authors.forename: Virve
authors.initials: V
authors.lastname: Koljonen
authors.affiliation: Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Haartmaninkatu 3, P.O. Box 21, FI-00014, Helsinki, Finland.
authors.forename: Tom
authors.initials: T
authors.lastname: Bohling
authors.affiliation: Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Haartmaninkatu 3, P.O. Box 21, FI-00014, Helsinki, Finland.
authors.forename: Mia
authors.initials: M
authors.lastname: Kero
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, FI-00014, Helsinki, Finland.
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, FI-00014, Helsinki, Finland.
authors.forename: Virinder Kaur
authors.initials: VK
authors.lastname: Sarhadi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics*; D015266:Carcinoma, Merkel Cell / Q000235:genetics* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000090243:Nucleophosmin; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; EZH2; Merkel cell carcinoma; Next-generation sequencing; RNA