title: Establishment of a novel cellular model for myxofibrosarcoma heterogeneity.
abstract: Human cancers frequently display substantial intra-tumoural heterogeneity in virtually all distinguishable phenotypic features, such as cellular morphology, gene expression, and metastatic potential. In order to investigate tumour heterogeneity in myxofibrosarcoma, we established a novel myxofibrosarcoma cell line with two well defined sub-clones named MUG-Myx2a and MUG-Myx2b. The parental tumour tissue and both MUG-Myx2 cell lines showed the same STR profile. The fact that MUG-Myx2a showed higher proliferation activity, faster migration and enhanced tumourigenicity was of particular interest. NGS mutation analysis revealed corresponding mutations in the FGFR3, KIT, KDR and TP53 genes. In contrast, the MUG-Myx2a cell lines showed an additional PTEN mutation. Analysis of CNV uncovered a highly aberrant karyotype with frequent losses and gains in the tumour sample. The two MUG-Myx2 cell lines share several CNV features of the tumour tissue, while some CNVs are present only in the two cell lines. Furthermore, certain CNV gains and losses that are exclusive to either MUG-Myx2a or MUG-Myx2b, distinguish the two cell lines. As it is currently not possible to purchase two different sarcoma cell lines derived from the same patient, the novel myxofibrosarcoma cell lines MUG-Myx2a and MUG-Myx2b will be useful tools to study pathogenesis, tumour heterogeneity and treatment options.
authors.affiliation: Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.affiliation: Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stuendl
authors.affiliation: Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.affiliation: Biomedical Research, Medical University of Graz, Graz, Austria.
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sauer
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Kashofer
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl-Atzwanger
mesh_terms: D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics; D002999:Clone Cells; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D018740:Genetic Heterogeneity; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D008954:Models, Biological
chemical_list: D000970:Antineoplastic Agents