title: Prevalence and implications of TERT promoter mutation in uveal and conjunctival melanoma and in benign and premalignant conjunctival melanocytic lesions.
abstract: OBJECTIVE
  Hot-spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in cutaneous and conjunctival melanoma and are exceedingly rare in uveal melanoma. No information is available on the presence of these mutations in the conjunctival melanocytic precursor lesion primary acquired melanosis (PAM). We tested a cohort of uveal and conjunctival melanomas as well as conjunctival benign and premalignant melanocytic lesions for TERT promoter mutations in order to elucidate the role of these mutations in tumor progression.
  
  
  METHODS
  TERT promoter mutation analysis on fresh tumor DNA and DNA from formalin-fixed, paraffin-embedded specimens was performed by SNaPshot analysis in 102 uveal melanomas, 39 conjunctival melanomas, 26 PAM with atypia, 14 PAM without atypia, and 56 conjunctival nevi.
  
  
  RESULTS
  Mutations of the TERT promoter were not identified in conjunctival nevi or PAM without atypia, but were detected in 2/25 (8%) of PAM with atypia and 16/39 (41%) of conjunctival melanomas. A single TERT promoter mutation was detected in 102 uveal melanomas (1%).
  
  
  CONCLUSIONS
  We present the second documented case of TERT promoter mutation in uveal melanoma. In comparison with other types of melanoma, TERT promoter mutations occur at extremely low frequency in uveal melanoma. TERT promoter mutations are frequent in conjunctival melanoma and occur at lower frequency in PAM with atypia but were not detected in benign conjunctival melanocytic lesions. These findings favor a pathogenetic tumor progression role for TERT promoter mutations in conjunctival melanocytic lesions.
authors.affiliation: Department of Ophthalmology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Koopmans
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Ober
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Hendrikus J
authors.initials: HJ
authors.lastname: Dubbink
authors.affiliation: The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: Dion
authors.initials: D
authors.lastname: Paridaens
authors.affiliation: Department of Ophthalmology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Naus
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Belunek
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Krist
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Edward
authors.initials: E
authors.lastname: Post
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.affiliation: Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Verdijk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003230:Conjunctival Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008548:Melanosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009508:Nevus, Pigmented / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D014604:Uveal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D000098943:Uveal Melanoma
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF; TERT; conjunctival melanoma; mutation; nevus; primary acquired melanosis; uveal melanoma