Table 1.
Genes identified as being significantly mutated or subject to focal copy number change in bladder cancer
| Genes identified as signficantly mutated | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Category | Total # mutations | % samples with mutations | # mutations NMIBC | % NMIBC | # mutations invasive | % invasive | Higher in NMIBC p= | Higher in NMIBC q= | Higher in invasive p= | Higher in invasive q= |
| TP53 | cell cycle | 176 | 44% | 12 | 22% | 164 | 47% | 0.9999 | 1 | 0.0004 | 0.01584 |
| HRAS | RAS | 26 | 6% | 5 | 9% | 21 | 6% | 0.2577 | 1 | 0.8829 | 0.9586 |
| ELF3 | transcription | 41 | 10% | 4 | 7% | 37 | 11% | 0.8305 | 1 | 0.3318 | 0.6532 |
| KDM6A | chromatin | 105 | 26% | 23 | 43% | 82 | 23% | 0.0032 | 0.1229 | 0.9988 | 0.9988 |
| ZFP36L1 | transcription | 28 | 7% | 2 | 4% | 26 | 7% | 0.9122 | 1 | 0.2477 | 0.5945 |
| CDKN1A | cell cycle | 33 | 8% | 1 | 2% | 32 | 9% | 0.9929 | 1 | 0.0468 | 0.3332 |
| RB1 | cell cycle | 66 | 16% | 5 | 9% | 61 | 17% | 0.9637 | 1 | 0.0894 | 0.4246 |
| PIK3CA | PI3K-mTOR | 84 | 21% | 13 | 24% | 71 | 20% | 0.3162 | 1 | 0.7960 | 0.9452 |
| ARID1A | chromatin | 94 | 23% | 11 | 20% | 83 | 24% | 0.7588 | 1 | 0.3640 | 0.6587 |
| ERCC2 | DNA repair | 41 | 10% | 3 | 6% | 38 | 11% | 0.9354 | 1 | 0.1695 | 0.5482 |
| CDKN2A | cell cycle | 20 | 5% | 0 | 0% | 20 | 6% | 1 | 1 | 0.0526 | 0.3332 |
| STAG2 | chr. segregation | 52 | 13% | 11 | 20% | 41 | 12% | 0.0658 | 0.8339 | 0.9713 | 0.9988 |
| FGFR3 | RTK | 51 | 13% | 12 | 22% | 39 | 11% | 0.0247 | 0.4692 | 0.9907 | 0.9988 |
| EP300 | chromatin | 54 | 13% | 9 | 17% | 45 | 13% | 0.2819 | 1 | 0.8375 | 0.9543 |
| RXRA | transcription | 27 | 7% | 4 | 7% | 23 | 7% | 0.4997 | 1 | 0.7145 | 0.8776 |
| RHOB | migration | 18 | 4% | 2 | 4% | 16 | 5% | 0.7212 | 1 | 0.5589 | 0.8249 |
| RHOA | migration | 18 | 4% | 2 | 4% | 16 | 5% | 0.7212 | 1 | 0.5589 | 0.8249 |
| TYRO3 | RTK | 14 | 3% | 1 | 2% | 13 | 4% | 0.8705 | 1 | 0.4199 | 0.7253 |
| MLL2 | chromatin | 70 | 17% | 3 | 6% | 67 | 19% | 0.9999 | 1 | 0.00704 | 0.13369 |
| KRAS | RAS | 14 | 3% | 2 | 4% | 12 | 3% | 0.5801 | 1 | 0.7159 | 0.8776 |
| ERBB3 | RTK | 43 | 11% | 2 | 4% | 41 | 12% | 0.9877 | 1 | 0.0514 | 0.3332 |
| TGFBR1 | RTK | 12 | 3% | 0 | 0% | 12 | 3% | 1 | 1 | 0.1742 | 0.5482 |
| ERBB2 | RTK | 37 | 9% | 5 | 9% | 32 | 9% | 0.5695 | 1 | 0.6284 | 0.8776 |
| KLF5 | transcription | 19 | 5% | 1 | 2% | 18 | 5% | 0.9388 | 1 | 0.2503 | 0.5945 |
| FAM47C | other | 15 | 4% | 2 | 4% | 13 | 4% | 0.6196 | 1 | 0.6764 | 0.8776 |
| BRWD1 | chromatin | 18 | 4% | 1 | 2% | 17 | 5% | 0.9289 | 1 | 0.2788 | 0.6233 |
| ERBB4 | RTK | 25 | 6% | 1 | 2% | 24 | 7% | 0.9754 | 1 | 0.1262 | 0.5330 |
| IRS4 | RTK | 8 | 2% | 0 | 0% | 8 | 2% | 1 | 1 | 0.3139 | 0.6532 |
| TXNIP | ROS regulation | 16 | 4% | 1 | 2% | 15 | 4% | 0.9039 | 1 | 0.3438 | 0.6532 |
| TSC1 | PI3K-mTOR | 25 | 6% | 3 | 6% | 22 | 6% | 0.6760 | 1 | 0.5644 | 0.8249 |
| NFE2L2 | transcription | 17 | 4% | 0 | 0% | 17 | 5% | 1 | 1 | 0.0827 | 0.4246 |
| CHIT1 | other | 11 | 3% | 0 | 0% | 11 | 3% | 1 | 1 | 0.2020 | 0.5482 |
| C3orf70 | other | 13 | 3% | 0 | 0% | 13 | 4% | 1 | 1 | 0.1502 | 0.5482 |
| MBD1 | chromatin | 11 | 3% | 0 | 0% | 11 | 3% | 1 | 1 | 0.2020 | 0.5482 |
| RAS* | RAS | 40 | 10% | 7 | 13% | 33 | 9% | 0.2753 | 1 | 0.8539 | 0.9543 |
| RHO* | migration | 36 | 9% | 4 | 7% | 32 | 9% | 0.7396 | 1 | 0.4572 | 0.7554 |
| Genes subject to focal copy number change | |||
|---|---|---|---|
| Gene symbol | Category | Total # focal CN change | % samples with focal CN change |
| ARID1A | chromatin | 12 | 5 |
| BCL2L1 | apoptosis | 24 | 10 |
| BEND3 | chromatin | 8 | 3 |
| BIRC3 | apoptosis | 10 | 4 |
| CCND1 | cell cycle | 26 | 11 |
| CCNE1 | cell cycle | 22 | 9 |
| CDKN2A | cell cycle | 100 | 43 |
| CREBBP | chromatin | 38 | 16 |
| E2F3 | Elongation factor | 43 | 18 |
| EGFR | RTK | 17 | 7 |
| ERBB2 | RTK | 12 | 5 |
| CCSER1 | mitosis | 36 | 15 |
| FGFR3 | RTK | 10 | 4 |
| FHIT | Fragile site | 30 | 13 |
| FOXQ1 | transcription | 25 | 11 |
| GDI2 | migration | 20 | 9 |
| IKZF2 | transcription | 35 | 15 |
| LRP1B | migration | 39 | 17 |
| MDM2 | cell cycle | 21 | 9 |
| MYC | transcription | 31 | 13 |
| MYCL | transcription | 13 | 6 |
| NCOR1 | chromatin | 57 | 24 |
| PDE4D | cAMP | 52 | 22 |
| PPARG | transcription | 34 | 14 |
| PRKCI | protein kinase C, | 9 | 4 |
| PTEN | PI3K-MTOR | 30 | 13 |
| Matrix | |||
| PVRL4 | interactions | 40 | 17 |
| RB1 | cell cycle | 39 | 17 |
| SOX4 | transcription | 42 | 18 |
| WWOX | other | 35 | 15 |
| YWHAZ | 14-3-3-zeta | 51 | 22 |
| ZNF703 | transcription | 24 | 10 |
Top: Genes identified as being significantly mutated or subject to focal copy number change in bladder cancer. Genes identified as significantly mutated in bladder cancer (Mutsig 2CV (20)) from analysis of 404 bladder cancers (350 invasive and 54 non-muscle invasive), as described in the Fig. 1 legend and text. The different colors in the “Category” column for genes identified as being significantly mutated indicate the different functional categories of genes with mutations. The green color in the other columns highlights those p values that are nominally significant (p < 0.05), and those q values that are significant (q < 0.2).
Bottom: Genes identified as involved in copy number change, either amplification or deletion, as identified by GISTIC2.0 (21). The red color in the “Gene symbol” column for genes subject to copy number change denotes amplification; blue denotes deletion. Again, the different colors in the “Category” column highlight the different functional categories of genes with mutations.
The asterisk denotes union of mutations of the types indicated:
RAS means KRAS or HRAS
RHO means RHOA or RHOB
Abbreviations: chr. segregation, chromosome segregation; RTK, receptor tyrosine kinase.