Table 1.
Amplifications in cancer-critical genes
| Cancer-critical genes with focal amplificationsa | Genomic region | Inhouse cohort, n = 203 MSS tumors | TCGA cohort, n = 320 MSS tumors | ||||||
|---|---|---|---|---|---|---|---|---|---|
| ≥15 additional copies | ≥ 5 additional copies | ≥15 additional copies | ≥5 additional copies | ||||||
| Amplification frequency, % [95% CI]* | CMS type | Amplification frequency, % [95% CI] | CMS type | Amplification frequency, % [95% CI] | CMS type | Amplification frequency, % [95% CI] | CMS type | ||
| ERBB2 | 17q12-q21.1 | 1.5 [0.5–4.3] | CMS2/2/3 | 1.5 [0.5–4.3] | CMS2/2/3 | 2.8 [1.5–5.3] | CMS2/2/4/4/4/4/4/NA/NA | 2.8 [1.5–5.3] | CMS2/2/4/4/4/4/4/NA/NA |
| TOX3 / CASC16 | 16q12.1–12.2 | 1.5 [0.5–4.3] | CMS2/4/NA | 3.0 [1.4–6.3] | CMS2/2/2/4/ NA/NA | 0.3 [0.02–1.7] | CMS2 | 0.9 [0.3–2.7] | CMS2/3/4 |
| MYC | 8q24.21 | 1.0 [0.3–3.5] | CMS1/2 | 2.5 [1.1–5.6] | CMS1/1/2/2/ NA | 0.3 [0.02–1.7] | CMS3 | 2.2 [1.1–4.4] | CMS1/2/3/3/4/4/NA |
| CCND2 / FGF6 / FGF23 / DYRK4 | 12p13.32 | 1.0 [0.3–3.5] | CMS3/NA | 1.5 [0.5–4.3] | CMS3/NA/NA | 0.9 [0.3–2.7] | CMS2/2/4 | 1.9 [0.9–4.0] | CMS2/2/4/4/4/4 |
| ANXA11 b | 10q22.3-q23.1 | 1.0 [0.3–3.5] | CMS2/NA | 1.5 [0.5–4.3] | CMS2/NA/NA | 0.3 [0.02–1.7] | CMS4 | 0.9 [0.3–2.7] | CMS3/4/4 |
| CDK12/ LASP1 (same peak as ERBB2) | 17q12-q21.1 | 0.5 [0.03–2.7] | CMS2 | 0.5 [0.03–2.7] | CMS2 | 1.9 [0.9–4.0] | CMS2/2/4/4/4/NA | 1.9 [0.9–4.0] | CMS2/2/4/4/4/NA |
| CDX2 / FLT3 | 13q12.13-q12.3 | 0.5 [0.03–2.7] | NA | 1.0 [0.3–3.5] | CMS2/NA | 1.6 [0.7–3.6] | CMS2/2/2/4/4 | 4.7 [2.9–7.6] | CMS2/2/2/2/2/2/2/3/4/4/4/4/4/4/NA |
| ESR1 | 6q25.1 | 0.5 [0.03–2.7] | NA | 0.5 [0.03–2.7] | NA | – | – | – | – |
| ETV1 | 7p21.3–21.2 | 0.5 [0.03–2.7] | NA | 1.0 [0.3–3.5] | NA/NA | – | – | – | – |
| FGFR1 | 8p11.23–11.22 | 0.5 [0.03–2.7] | CMS3 | 2.0 [0.8–5.0] | CMS2/2/2/3 | – | – | 2.2 [1.1–4.4] | CMS2/2/2/2/2/4/4 |
| MUTYH | 1p34.1 | 0.5 [0.03–2.7] | CMS2 | 0.5 [0.03–2.7] | CMS2 | – | – | – | – |
| NDRG1 | 8q24.22 | 0.5 [0.03–2.7] | CMS1 | 2.5 [1.1–5.6] | CMS1/1/2/NA/NA | 0.3 [0.02–1.7] | CMS3 | 0.9 [0.3–2.7] | CMS2/3/4 |
| RARA / SMARCE1 (same peak as ERBB2) | 17q12-q21.1 | 0.5 [0.03–2.7] | CMS2 | 0.5 [0.03–2.7] | CMS2 | 0.6 [0.2–2.2] | CMS2/4 | 1.3 [0.5–3.2] | CMS2/2/4/NA |
| SUZ12 | 17q11.2 | 0.5 [0.03–2.7] | CMS3 | 0.5 [0.03–2.7] | CMS3 | – | – | – | – |
| SYK | 9q22.2–22.31 | 0.5 [0.03–2.7] | CMS4 | 0.5 [0.03–2.7] | CMS4 | – | – | – | – |
| TOP1 | 20q12 | 0.5 [0.03–2.7] | CMS2 | 1.0 [0.3–3.5] | CMS2/NA | – | – | 2.5 [1.3–4.9] | CMS2/2/2/2/4/4/NA/NA |
aFocal amplifications were defined as peaks encompassing <50 genes
bNot included in the COSMIC cancer census. The gene was nominated based on available literature along with gene expression levels of genes in the amplified peak
*CI: 95% binomial confidence intervals using the Wilson method