Extended Data Fig. 4: Copy number changes in TA-UC.

(a) TA-UC samples are grouped according to mutated genes in Fig. 1b, with each column representing one tumor. Top: Sample identifiers of the TA-UC discovery cohort; molecular (MSI, microsatellite instability; CIN, chromosomally instability; GS, genomically stable; POLE, polymerase ε) and histological classifications; ABSOLUTE-generated ploidy values; presence of whole-genome doubling (WGD). Middle: ABSOLUTE total copy numbers of individual segments delineated by their genomic position along the 22 chromosomes (top to bottom); colors indicate loss, copy neutral loss-of-heterozygosity (LOH) or gain at genomic loci. Bottom: colored boxes indicate presence of a mutation; bars on the right of the boxes depict cancer cell fraction (CCF); significantly mutated genes are shown in bold as in Fig. 1b; genes of the PI3K pathway are in violet. (b) Amplifications (left, red) and deletions (right; blue) detected by GISTIC in the TA-UC discovery cohort. Chromosomal positions from top to bottom; Q-values from left to right (green line, Q < 0.25). Significant peaks are annotated with chromosomal position and candidate cancer genes, where applicable (black); positions of non-significant genes of the PI3K pathway are also annotated (gray). (c) Bar plot of tumors with genomic alterations in key PI3K pathway genes including single-nucleotide variants (mut) and somatic copy number alterations (gain/deletion); only TCGA tumors with both data types considered; genes altered by either type counted once per tumor; bars represent mutation frequencies, with genes ordered by P-value (top to bottom); error bars reflect standard deviation from the β-distribution; significance analysis by two-sided Fisher’s exact test with and without Benjamini-Hochberg procedure; numbers in bars indicate mutated tumor count per group.