title: Specific analysis of KIT and PDGFR-alpha expression and mutational status in Merkel cell carcinoma.
abstract: BACKGROUND
  The purpose of this study was to explore the immunohistochemical and mutational status of the tyrosine kinases KIT and platelet derived growth receptor-alpha (PDGFRA) in Merkel cell carcinoma (MCC). Specifically, we examined the mutated exons in gastrointestinal stromal cell tumors that may confer a treatment response to imatinib mesylate.
  
  
  METHODS
  We evaluated KIT and PDGFRA immunostaining in 23 examples of MCC utilizing laser capture microdissection to obtain pure samples of tumor genomic DNA from 18 of 23 examples of MCC. PCR amplification and sequencing of KIT exons 9, 11, 13 and 17, and PDGFRA exons 10, 12, 14 and 18 for mutations was performed.
  
  
  RESULTS
  Fifteen of 23 tumors (65%) demonstrated CD117 expression and 22 of 23 tumors (95%) demonstrated PDGFRA expression. A single heterozygous KIT exon 11 base change resulting in an E583K mutation was discovered in 12 of 18 (66%) examples of MCC. In addition, a single nucleotide polymorphism was detected in eight of 18 tumors (44%) in exon 18 of PDGFRA (codon 824; GTC > GTT).
  
  
  CONCLUSIONS
  We discovered a novel somatic KIT exon 11 E583K mutation in 66% of tumors. This mutation has been previously described in a human with piebaldism and appears to represent an inactivating mutation. Therefore, despite expression of CD117 and PDGFRA, the absence of activating mutations in these tyrosine kinases makes KIT and PDGFRA unlikely candidates of MCC oncogenesis.
authors.affiliation: Department of Dermatology, University of Iowa, Iowa City, IA 52242, USA. swickbrian@yahoo.com
authors.forename: Brian L
authors.initials: BL
authors.lastname: Swick
authors.forename: Rupasree
authors.initials: R
authors.lastname: Srikantha
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Messingham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D015266:Carcinoma, Merkel Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003062:Codon / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010879:Piperazines / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D003062:Codon; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha