Figure 1

Genomic aberrations in cancer. Three classes of genomic aberration that develop in cancer cells are depicted: mutations of less than 1 Kbp in length (top box), structural copy number aberrations (CNAs) (bottom left box), and structural rearrangements (bottom right box). The initial state in the germline is shown followed by the corresponding change in the tumor. Mutations that affect regions of less than 1 Kbp are of three basic types: substitutions, of which there are transversions and transitions; insertions; and deletions. Insertions and deletions are often collectively termed ‘indels’. Structural CNAs are typically greater than 1 Kbp in size. One of the basic types is copy number gain. The two homologous chromosomes are shown with a gain of two further copies of region A on the paternal chromosome leading to an imbalance in the allelic ratio (1:3, maternal: paternal). The gained region is highlighted by the green bar adjacent to paternal region A. Copy number loss of regions A and B on the paternal chromosome is shown with a red bar highlighting the deleted regions. Three of the commonest types of structural rearrangement are shown, with the letters A to D and X to Z depicting defined chromosomal segments. An inversion on the same chromosome results in a change to the orientation of DNA sequences on the same chromosome either paracentrically (without crossing the centromere) or pericentrically (crossing the centromere). The inverted sequences in the tumor are shown in red. Translocations can be reciprocal or non-reciprocal and typically occur between non-homologous chromosomes (the green and blue chromosomes are non-homologous). A reciprocal translocation is shown with regions A and B exchanged for regions X and Y. Recombinations typically occur between sister chromatids where they are conservative, but can occur between homologous chromosomes (the green and purple chromosomes are homologous with green being the maternal, and purple the paternal) where recombinations at a heterozygous allelic locus can lead to cnLOH. The dotted boxes indicate where these aberrations are detectable by single-nucleotide polymorphism microarrays, whereas the grey dashed line encompasses those that can also be captured by array comparative genomic hybridization (aCGH), which does not distinguish between alleles. All forms of aberration may be interrogated by using sequencing. A, adenine; C, cytosine; cnLOH, copy number-neutral loss of heterozygosity; G, guanine; LOH, loss of heterozygosity; T, thymine.