Establishment and characterization of a panel of human uveal melanoma xenografts derived from primary and/or metastatic tumors.
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.
Némati
Fariba
F
Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, Paris, France.
Sastre-Garau
Xavier
X
Laurent
Cécile
C
Couturier
Jérôme
J
Mariani
Pascale
P
Desjardins
Laurence
L
Piperno-Neumann
Sophie
S
Lantz
Olivier
O
Asselain
Bernard
B
Plancher
Corine
C
Robert
Delphine
D
Péguillet
Isabelle
I
Donnadieu
Marie-Hélène
MH
Dahmani
Ahmed
A
Bessard
Marie-Andrée
MA
Gentien
David
D
Reyes
Cécile
C
Saule
Simon
S
Barillot
Emmanuel
E
Roman-Roman
Sergio
S
Decaudin
Didier
D
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
D014408:Biomarkers, Tumor; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide