title: Patient-derived xenografts recapitulate molecular features of human uveal melanomas.
abstract: We have previously developed a new method for the development and maintenance of uveal melanoma (UM) xenografts in immunodeficient mice. Here, we compare the genetic profiles of the primary tumors to their corresponding xenografts that have been passaged over time. The study included sixteen primary UMs and corresponding xenografts at very early (P1), early (P4), and late (P9) in vivo passages. The tumors were analyzed for mutation status of GNAQ, GNA11, GNAS, GNA15, BAP1, and BRAF, chromosomal copy number alterations using Affymetrix GeneChip(®) Genome-Wide Human SNP6.0 arrays, gene expression profiles using GeneChip(®) Human Exon 1.0 ST arrays, BAP1 mRNA and protein expression, and MAPK pathway status using Reverse Phase Protein Arrays (RPPA). The UM xenografts accurately recapitulated the genetic features of primary human UMs and they exhibited genetic stability over the course of their in vivo maintenance. Our technique for establishing and maintaining primary UMs as xenograft tumors in immunodeficient mice exhibit a high degree of genetic conservation between the primary tumors and the xenograft tumors over multiple passages in vivo. These models therefore constitute valuable preclinical tool for drug screening in UM.
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Laurent
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.forename: Fariba
authors.initials: F
authors.lastname: Némati
authors.forename: André
authors.initials: A
authors.lastname: Nicolas
authors.forename: Bruno
authors.initials: B
authors.lastname: Tesson
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.forename: Pascale
authors.initials: P
authors.lastname: Mariani
authors.forename: Audrey
authors.initials: A
authors.lastname: Rapinat
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.forename: Leanne
authors.initials: L
authors.lastname: de Koning
authors.forename: Thierry
authors.initials: T
authors.lastname: Dubois
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: J William
authors.initials: JW
authors.lastname: Harbour
authors.forename: Simon
authors.initials: S
authors.lastname: Saule
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: C400134:BAP1 protein, human; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D025521:Tumor Suppressor Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D043222:Ubiquitin Thiolesterase; D043802:GTP-Binding Protein alpha Subunits, Gq-G11