The development and progression of cancer is often associated with the acquisition of nonrandom chromosome aberrations. These can produce changes in gene loci, resulting in either the deregulated expression of an oncogene, the production of a chimaeric fusion gene or inactivation of a tumour suppressor gene (TSG). Chromosome aberrations are particularly important in the diagnosis, prognosis, progression, monitoring and treatment of acute and chronic leukaemia, small round cell tumours and central nervous system tumours. Numerical chromosome changes typically result in gain or loss of a few chromosomes, but can also produce changes in ploidy. Translocations, mostly affecting oncogenes, account for the majority of disease-specific structural chromosome aberrations, whereas deletions are more important in TSGs. Knowledge of the nature and mechanisms of action of the genes involved is important in understanding how they contribute to the genesis, promotion and progression of this complex disease.

Key concepts

• Chimaeric gene fusion – the most frequent, recurrent oncogenic change usually produced via chromosome translocation. Two previously separate and independent genes are fused to form a single unique contiguous gene, and the resultant gene product has oncogenic properties.
  
• Oncogene deregulation – juxtapositioning of an oncogene with the enhancer region of a T-cell receptor gene or an Immunoglobulin gene results in overexpression of the oncogene protein product. This is most commonly a result of a chromosome translocation.
  
• Oncogene amplification – a selective, unscheduled increase in gene copy number enabling a cell to meet the increased transcriptional demands of neoplastic transformation. This is seen as double minutes or as a chromosome duplication.
  
• Tumour suppressor gene inactivation – removal of the growth control functions of a TSG either by mutation or loss, after which the cell may fail to keep a cancer from developing, transforming the cell to a cancer phenotype.
  
• Loss of heterozygosity – the key mechanism of inactivation of a TSG. At a locus heterozygous for a deleterious mutant allele and a normal allele, a deletion or other mutation in the normal allele renders the cell hemizygous or homozygous for the deleterious allele.