title: Different TP53 mutations are associated with specific chromosomal rearrangements, telomere length changes, and remodeling of the nuclear architecture of telomeres.
abstract: TP53 mutations are the most common mutations in human cancers, and TP53-R175H and TP53-R273H are the most frequent. The impact of these mutations on genomic instability after tumor initiation is still uncovered. To gain insight into this, we studied the effects of three specific TP53 mutants (TP53-V143A, TP53-R175H, and TP53-R273H) on genomic instability using four isogenic lines of LoVo cells. Multicolor fluorescence in situ hybridization (FISH), three-dimensional (3D) quantitative FISH (Q-FISH) on interphase and Q-FISH on metaphases were used to investigate genomic instability. We found that LoVo cells expressing mutant TP53-R175H displayed the highest level of chromosomal instability among the LoVo cell lines. Furthermore, we observed that mutant TP53-R175H and TP53-V143A showed more alterations in their 3D nuclear architecture of telomeres than the mutant TP53-R273H and the wild type. Moreover, we noted an association between some chromosomal abnormalities and telomere elongation in the mutant TP53-R175H. Taken together, our results indicate that the mutation TP53-R175H is more likely to cause higher levels of genomic instability than the other TP53 mutations. We proposed that the type of TP53 mutations and the genetic background of a cancer cell are major determinants of the TP53-dependent genomic instability.
authors: Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors: Oumar
authors: O
authors: Samassekou
authors: Nathalie
authors: N
authors: Bastien
authors: Daniel
authors: D
authors: Lichtensztejn
authors: Ju
authors: J
authors: Yan
authors: Sabine
authors: S
authors: Mai
authors: Régen
authors: R
authors: Drouin
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D043171:Chromosomal Instability; D003110:Colonic Neoplasms; D006801:Humans; D009154:Mutation; D000089804:Shelterin Complex; D016615:Telomere / Q000648:ultrastructure*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000089804:Shelterin Complex; C495901:TP53 protein, human; D034501:Telomere-Binding Proteins; D016159:Tumor Suppressor Protein p53