title: Establishment and characterization of a panel of human uveal melanoma xenografts derived from primary and/or metastatic tumors.
abstract: OBJECTIVE
  Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice.
  
  
  METHODS
  Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma.
  
  
  RESULTS
  Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents.
  
  
  CONCLUSIONS
  Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments.
authors.affiliation: Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, Paris, France.
authors.forename: Fariba
authors.initials: F
authors.lastname: Némati
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Cécile
authors.initials: C
authors.lastname: Laurent
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Pascale
authors.initials: P
authors.lastname: Mariani
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Corine
authors.initials: C
authors.lastname: Plancher
authors.forename: Delphine
authors.initials: D
authors.lastname: Robert
authors.forename: Isabelle
authors.initials: I
authors.lastname: Péguillet
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Donnadieu
authors.forename: Ahmed
authors.initials: A
authors.lastname: Dahmani
authors.forename: Marie-Andrée
authors.initials: MA
authors.lastname: Bessard
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.forename: Cécile
authors.initials: C
authors.lastname: Reyes
authors.forename: Simon
authors.initials: S
authors.lastname: Saule
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D020411:Oligonucleotide Array Sequence Analysis; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D000077204:Temozolomide; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide