Back to Search
Start Over
Patient-derived xenografts recapitulate molecular features of human uveal melanomas
- Source :
- Molecular Oncology. 7:625-636
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
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.
- Subjects :
- Proto-Oncogene Proteins B-raf
Uveal Neoplasms
Cancer Research
MAP Kinase Signaling System
DNA Mutational Analysis
medicine.disease_cause
Mice
In vivo
Tumor Cells, Cultured
Genetics
GNAS complex locus
medicine
Animals
Humans
Melanoma
Oligonucleotide Array Sequence Analysis
BAP1
Mutation
GNA11
biology
Tumor Suppressor Proteins
General Medicine
medicine.disease
GTP-Binding Protein alpha Subunits
Gene Expression Regulation, Neoplastic
Gene expression profiling
Oncology
Papers
biology.protein
Cancer research
GTP-Binding Protein alpha Subunits, Gq-G11
Heterografts
Molecular Medicine
Transcriptome
Ubiquitin Thiolesterase
GNAQ
Subjects
Details
- ISSN :
- 15747891
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecular Oncology
- Accession number :
- edsair.doi.dedup.....3424543b00f44efe4cb997377c1e2ce2