Table 3.
Previously Reported TSC mutations in Renal Cell Carcinoma
| Chromophobe RCC (n=164) |
Clear Cell RCC (n=578) |
Clear Cell RCC w Sarcomaoid Features (n=106) | Renal Non-Clear Cell RCC (n=146)*34 | High Grade Unclassified RCC (n=62)39 |
|
|---|---|---|---|---|---|
|
| |||||
| Total TSC-Mutated Cases/Pts | 4 (2.4%) | 12 (2.1%) | 2 (1.9%) | 5 (3.4%) | 7 (11.3%) |
|
| |||||
| TSC1-Mutated | 3 (1.8%) | 3 (0.5%) | 1 (0.9%) | 3 (2.1%) | 4 (6.5%) |
| TSC2-Mutated | 1 (0.6%) | 9 (1.6%) | 1 (0.9%) | 2 (1.4%) | 3 (4.8%) |
|
| |||||
| Reported TSC1 Mutations | n=3 | n=3 | n=1 | n=3 | n=4 |
|
| |||||
| Frameshift | 1 | 1 | 0 | 0 | 2 |
|
| |||||
| Nonsense | 1 | 0 | 0 | 0 | 1 |
|
| |||||
| Splice site | 1 | 0 | 0 | 0 | 0 |
|
| |||||
| Missense | 0 | 2 | 1 | 3 | 1 |
|
| |||||
| Reported TSC2 Mutations | n=1 | n=10 | n=1 | n=3 | n=4 |
|
| |||||
| Frameshift | 0 | 0 | 1 | 1 | 0 |
|
| |||||
| Nonsense | 0 | 5 | 0 | 1 | 2 |
|
| |||||
| Splice site | 0 | 1 | 0 | 0 | 0 |
|
| |||||
| Missense | 1 | 4 | 0 | 1 | 2 |
Two cases from the renal non-clear cell RCC cohort34 were annotated as classic chromophobes: one case with a TSC1 missense mutation; and the other case with one TSC2 frameshift mutation and one TSC2 nonsense mutation. Three cases were annotated as “papillary”: two cases with one TSC1 missense mutation each; and the third case with one TSC2 missense mutation. This combined query contains samples from 7 studies: 1) Kidney Renal Clear Cell Carcinoma (BGI, Nat Genet 2012)35; 2) Clear Cell Renal Cell Carcinoma (U Tokyo, Nat Genet 2013)36; 3) Kidney Chromophobe (TCGA, Cancer Cell 2014)37; 4) Kidney Renal Clear Cell Carcinoma (TCGA, Nature 2013)33; 5) Renal Non-Clear Cell Carcinoma (Genentech, Nat Genet 2014)34; 6) Targeted gene sequencing in 62 high-grade primary Unclassified RCC (MSK, Nature 2016)39; and 7) Multiregion Sequencing of Clear Cell Renal Cell Carcinoma (IRC, Nat Genet 2014)38. The query was performed using cBioPortal for Cancer Genomics (www.cbioportal.org)40,41 accessed on Feb 15, 2018.