Figure 6

Monoallelic amplification in HER2-amplified breast cancer. (A) High-level amplifications predominantly show amplification of one parental chromosome in HER2-amplified breast cancer. Partitioned mBAF [12] estimates are plotted against corresponding partitioned CN values for 108 genomic segments > 50 kbp in size and with a partitioned log2ratio > 0.7 from cases in the Lund-HER2-SNP set, representing high-level amplification segments in this data set. The color and height of segments on the z-axis indicate chromosome location. BAF estimates range between 0 and 1 reflecting the proportion of the two parental chromosomes for a given SNP. Due to the symmetry of BAF profiles for current genome-wide SNP arrays, BAF profiles may be reflected along the central 0.5 axis into mBAF estimates [12]. In a normal sample mBAF values close to 0.5 represent a heterozygous state (AB) for a given SNP, whereas values close to 1 represent a homozygous state (AA or BB). In tumor samples allelic imbalances are seen as a deviation of heterozygous SNPs from 0.5. The amplitude of the deviation is a function of the type of aberration, fraction of aberrant cells carrying the aberration and tumor ploidy. Thus, for amplification events in tumor samples higher mBAF values indicate additional copies of one of the two parental chromosomes in the amplified region. (B) Distribution of estimated allele specific copy numbers from GAP analysis for 835 events in 90 of 99 samples analyzed by SNP arrays, > 2 Mbp in size and with a total CN > 3 compared to the GAP-ploidy for respective sample. The latter means that if the GAP-ploidy of a sample is 2.58 an event must have a total CN > 5.58 to be included. For each event on the x-axis allele specific copy numbers for the two parental chromosomes are shown as green and red bars. The total CN is the sum of the height of the red and green bars, and is truncated at eight by GAP. GAP returns allele specific copy numbers as numerical values, for example, 2.5, for possible identification of sub-clonal events, thus the steps in the plot are not discrete.