Figure 5.

Evolutionary sequential compound copy number analysis. (A) Analysis of proportion of the genome that was altered by sequential compound events. Compound events include copy neutral LOH (NLOH) and amplified LOH (ALOH) regions, which indicates the occurrence of more than one copy number event in sequence (eg deletion followed by amplification of remaining allele results in ALOH). (B) Pairwise comparison of copy number samples within case 3. The number of genes with a specific predicted discrete copy number (CN) is represented by the size of the dot. Genes that also have the same zygosity (LOH or heterozygous) status between the two samples are coloured red; otherwise they are grey. (C) Doubling of chromosome 18 in case 3b relative to case 3a. Deletion (green) in 18q in 3a is observed as NLOH (blue) in 3b; amplification of 18p in 3b is balanced, indicating doubling of both diploid alleles in 3a. ‘A’ and ‘B’ genotypes are used to denote the two alleles. (D) Phylogenetic tree of discrete compound events. Genes were assigned an integer value representing the weight of observing compound events: 2, ALOH; 2, NLOH; 2, homozygous deletion; 1, hemizygous deletion; 0, diploid heterozygous; 0, allele-specific amplification. Euclidean distance was computed between pairs of tumour samples and a control (which consists of zeros for all genes) and neighbour-joining cluster analysis was used to generate the tree.