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Chromosomal instability in HCC: a key function for checkpoint kinase 2
  1. Robert Eferl1,
  2. Michael Trauner2
  1. 1 Department for Internal Medicine I, Institute of Cancer Research, Medical University Vienna & Comprehensive Cancer Center (CCC), Vienna, Austria
  2. 2 Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Dr Robert Eferl, Institute of Cancer Research, Medical University Vienna & Comprehensive Cancer Center (CCC), Borschkegasse 8a, A-1090 Vienna, Austria; robert.eferl{at}meduniwien.ac.at

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The German cytologist Theodor Boveri proposed about 100 years ago that cancer is caused by an abnormal distribution of microscopic bodies called chromosomes. At that time, researchers had no idea of the cellular component for inheritance and challenged his hypothesis. Meanwhile, genomic instability is viewed as a hallmark of cancer1 and an alternative model for cancer formation was put forward that proposed acquisition of a ‘mutator’ phenotype as the initiating event. Although supported by the vast plasticity of sequence changes and chromosomal aberrations in individual cells of single tumours, these observations did not solve the issue whether the ‘mutator’ phenotype is a precondition or a consequence of tumourigenesis.

The ‘mutator’ phenotype is causative for genomic instability, an umbrella term for small DNA structure variations, microsatellite instability and chromosomal instability (CIN).2 The latter affects chromosome number and structure and is a characteristic feature of many cancer types including hepatocellular carcinoma (HCC).3 It is also associated with the formation of extranuclear bodies that contain damaged chromosome fragments or whole chromosomes. Such micronuclei were identified in regenerative and dysplastic nodules of the liver indicating that CIN can be acquired already in early stage hepatocarcinogenesis.3 Apparently, CIN is linked to certain cancer genotypes because HCC has been originally divided into two major subclasses: one displaying a stable cancer genome and activating β-catenin mutations, and the other with extensive CIN, p53 and Axin …

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