Figure 3

Mutation landscape in invasive micropapillary carcinoma according to grade, genomic subgroup and phenotype and pathway interactions between the 23 mutated genes. (A) Distribution of validated somatic mutations among the 50 cases as determined by whole-exome sequencing, targeted MiSeq sequencing and classical Sanger sequencing (TP53, PIK3CA, SEC63 and FOXO3). Central heatmap: distribution of significant mutations across sequenced samples with color-coding according to the allelic genomic status determined by Affymetrix Genome-Wide Human SNP 6.0 Array analysis. Yellow = neutral copy number; green = deletion, dark pink = gain. Upper chart color-coding from top to bottom: chromosome 6q allelic status (light green = loss of heterozygosity; dark green = deletion), tumour ploidy (dark purple = tetraploid; light purple = diploid), invasive micropapillary carcinoma (IMPC) genomic group (red = “Firestorm/Amplifier”; green = “Sawtooth/8/16”), oestrogen receptor (ER) status (dark blue = positive), ERBB2 overexpression (orange = positive 3+), grade (light grey = grade 1; intermediate grey = grade 2; dark grey = grade 3), axillary lymph node status (dark = N+). Chr, chromosome; ND, Not determined. Function is defined according to the Gene Ontology database and UCSC Genome Browser. (B) Interactions and pathways between the 23 mutated genes in IMPCs deduced from the Reactome algorithm [38]. In this diagram, the functional interaction (FI) network connections are symbolised by arrows for activating/catalysing, solid lines ending in perpendicular line for inhibition, solid lines for FIs extracted from complexes or inputs, dashed lines for predicted FIs and dotted lines for defined FIs.