Table 1.
Summary of major publications documenting STAG2 mutations in bladder cancer and Ewing sarcoma.
| Samples tested | Original detection approachϕ | Frequency of samples harboring STAG2 mutations | Frequency of samples exhibiting STAG2 protein loss by IHC | Disease correlations | Genetic correlations with STAG2 mutation/loss | Other cohesin subunits affected by mutationΔ | Reference |
|---|---|---|---|---|---|---|---|
| Bladder tumors of various stages and grades and cell lines | IHC tissue microarray | 21% (n=111) tumors overall; 36% nonmuscle- invasive (n=25); 27% superficially invasive (n=22); 13% muscle- invasive (n=64); 16% cell lines(n=32) | 18% (n=295) | Higher rate of STAG2 mutation/loss in nonmuscle-invasive cancers | TP53 mutation and overexpression (co- occurrence) | Not performed | Solomon et al., 2013 [42] |
| Loss of STAG2 expression associated with better prognosis in nonmuscle- invasive cancers and worse prognosis in muscle-invasive cancers | No significant association with aneuploidy in tumors but some evidence in cell line experiments | ||||||
| Bladder tumors of various stages and grades (mostly nonmuscle- invasive) | WES | 16% (n=77) overall; 21% non- aggressive (n=29); 11% aggressive (n=47) | 29% (n=671) | Higher rate of STAG2 mutation/loss in nonmuscle-invasive tumors | No significant association with aneuploidy | STAG1 (8%); SMC1A (2%); SMC1B (3%); MAU2 (3%); RAD21 (2%); SMC3 (2%); NIPBL (2%); ESCO2 (2%); PDS5B (2%) (n=60) | Balbas-Martinez et al., 2013 [43] |
| Loss of STAG2 expression associated with better prognosis in both muscle- invasive and nonmuscle- invasive tumors | |||||||
| Bladder tumors of various stages and grades | WES | 11% (n=99) | Not performed | STAG2 mutation associated with worse prognosis | More aneuploidy in STAG2 mutant tumors | NIPBL (6%); SMC1A (3%); SMC3 (2%) (n=99) | Guo et al., 2013 [44] |
| Bladder tumors of various stages and grades and cell lines | Targeted single gene mutation analysis | 26% tumors (n=307); 17% cell lines (n=47) | Not performed | STAG2 mutation associated with low tumor grade and stage | Lower number of chromosomal copy number alterations in samples with STAG2 mutation | Not performed | Taylor et al., 2014 [45] |
| Muscle-invasive bladder tumors | WES/WGS | 11% (n=200) | Not performed | N/A | N/A | NIPBL (4%); RAD21 (3%); STAG1 (2%); SMC3 (2%); SMC1A (2%); SMC1B (2%); CDCA5 (2%); WAPL (2%); STAG3 (2%) (n=200) | TCGA, 2014 [46] |
| Ewing sarcoma tumors and cell lines | WGS | 22% tumors (n=65); 44% cell lines (n=36) | 14% (n=210) | STAG2 mutation associated with metastatic disease | TP53 mutation (co- occurrence - cell lines only) | Not detected (n=6) | Brohl et al., 2014 [50] |
| Ewing sarcoma tumors and cell lines | WES | 8% tumors (n=96); 36% cell lines (n=11) | 15% (n=73) | STAG2 mutation associated with metastatic disease | TP53 mutation (co- occurrence) | RAD21 (2%); PDS5B (2%); SMC1A (1%); NIPBL (1%); REC8 (1%); STAG3 (1%) (n=96) | Crompton et al., 2014 [51] |
| Ewing sarcoma tumors and cell lines | WGS | 15% tumors (n=411) 47% cell lines (n=19) | Not performed | N/A | TP53 mutation (co- occurrence) | STAG1 (<1%); SMC1A (<1%) (n=112) | Tirode et al., 2014 [52] |
| CDKN2A deletion (mutual exclusivity) |
This table provides an overview of the major findings regarding STAG2 mutation and expression loss in bladder cancer and Ewing sarcoma. Frequencies of other cohesin gene mutations are also shown.
This column describes the initial detection used to identify STAG2 mutations in each study.
Additional methods may have been used for prevalence screens. WES (whole exome sequencing); WGS (whole genome sequencing); IHC (immunohistochemistry).
Where additional cohesion genes were not discussed in the manuscript, available WES/WGS data or prevalence screen data was mined for mutations in the following genes: STAG1, STAG2, STAG3, RAD21, SMC3, SMC1A, SMC1B, NIPBL, CDCA5, WAPL, MAU2, ESCO1, ESCO2, PDS5A, PDS5B and REC8.