title: Chromosomal disruption and rearrangements during murine sarcoma development converge to stable karyotypic formation kept by telomerase overexpression.
abstract: BACKGROUND
  Tumor initiation presents a complex and unstable genomic landscape; one of the earliest hallmark events of cancer, and its progression is probably based on selection mechanisms under specific environments that lead to functional tumor cell speciation. We hypothesized that viable tumor phenotypes possess common and highly stable karyotypes and their proliferation is facilitated by an attuned high telomerase activity. Very few investigations have focused on the evolution of common chromosomal rearrangements associated to molecular events that result in functional phenotypes during tumor development.
  
  
  RESULTS
  We have used cytogenetic, flow cytometry and cell culture tools to investigate chromosomal rearrangements and clonality during cancer development using the murine sarcoma TG180 model, and also molecular biology techniques to establish a correlation between chromosome instability and telomerase activity, since telomeres are highly affected during cancer evolution. Cytogenetic analysis showed a near-tetraploid karyotype originated by endoreduplication. Chromosomal rearrangements were random events in response to in vitro conditions, but a stable karyotypic equilibrium was achieved during tumor progression in different in vivo conditions, suggesting that a specific microenvironment may stabilize the chromosomal number and architecture. Specific chromosome aberrations (marker chromosomes) and activated regions (rDNAs) were ubiquitous in the karyotype, suggesting that the conservation of these patterns may be advantageous for tumor progression. High telomerase expression was also correlated with the chromosomal rearrangements stabilization.
  
  
  CONCLUSIONS
  Our data reinforce the notion that the sarcoma cell evolution converges from a highly unstable karyotype to relatively stable and functional chromosome rearrangements, which are further enabled by telomerase overexpression.
authors: Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil. robson_junr@yahoo.com.br.
authors: Robson José
authors: RJ
authors: de Oliveira-Júnior
authors: Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil.
authors: Carlos
authors: C
authors: Ueira-Vieira
authors: Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil.
authors: Angela Aparecida Servino
authors: AA
authors: Sena
authors: Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil.
authors: Carolina Fernandes
authors: CF
authors: Reis
authors: Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil.
authors: José Roberto
authors: JR
authors: Mineo
authors: Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil. lrgoulart@ufu.br.|Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA. lrgoulart@ufu.br.
authors: Luiz Ricardo
authors: LR
authors: Goulart
authors: Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil. morelli@ufu.br.
authors: Sandra
authors: S
authors: Morelli
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012509:Sarcoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D009363:Neoplasm Proteins; D019098:Telomerase