Role of chromosomal instability in cancer progression

  1. Sarah E McClelland
  1. Barts Cancer Institute, Queen Mary University of London, London, UK
  1. Correspondence should be addressed to S E McClelland; Email: S.McClelland{at}
  1. Figure 1

    Chromosome segregation errors. (A) Cartoon illustrating the three major classes of chromosome segregation error. Lagging centric chromosomes, identified by antibodies targeting centromere-bound proteins, are likely to be whole chromosomes. Acentric fragments, lacking centromeric protein signals, and chromatin bridges, are likely to reflect structurally abnormal chromosomes. (B) Two types of incorrect kinetochore–microtubule attachment are shown, merotelic attachment where one or both sister kinetochores are attached to microtubules emanating from both centrosomes and syntelic attachment where both sister kinetochores are attached only to a single centrosome.

  2. Figure 2

    Major pathways to chemotherapy resistance. Three different but not necessarily mutually exclusive pathways to resistance are depicted. Innate resistance allows tumour growth to continue unchecked by the application of chemotherapy, for example, in the case of patients with non-responsive tumours. Acquired resistance can occur if a pre-existing tumour cell or clone is present in the primary tumour that is capable of survival in the presence of chemotherapy agent. Tumours will initially respond and regress, but relapse will occur, seeded from the resistant clones. Adaptive resistance occurs when genetic or other mechanisms allowing the development of novel traits is present. Chemotherapy itself may also promote genome mutation and rearrangement to facilitate this process. Cells that chance upon a resistant phenotype are then able to seed tumour regrowth. A prediction of these distinct pathways to resistance is that the relapsed tumour may display different levels of heterogeneity or CIN depending on which pathway was most prevalent during tumour regrowth.

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