Table 2.
Pathologic and tissue molecular characteristics of patient tumors by GNAS/GNAQ/GNA11 aberration status (n = 1348).*
| Characteristic | All patients (n = 1348) | GNA† wild type (n = 1293) | GNA† aberrant (n = 55) | P-value ** | Odds ratio (95% CI) |
|---|---|---|---|---|---|
| Histology | |||||
| Adenocarcinoma | 217 (16.1%) | 202 (15.6%) | 15 (27.3%) | 0.037 | 2.0 (1.0 to 3.8) |
| Squamous | 76 (5.6%) | 75 (5.8%) | 1 (1.8%) | 0.36 | |
| Metastatic | 1046/1258 (83.1%) | 1003/1210 (82.9%) | 43/47 (91.5%) | 0.16 | |
| Number of aberrations (including VUSs) (median, IQR) | 10 (4 to 15) | 9 (4 to 14) | 17 (12 to 26) | <2.2–16 | Not applicable |
| Number of characterized aberrations (excludes VUSs) (median, IQR) | 3 (2 to 6) | 3 (2 to 5) | 6 (3 to 9) | 2.50–6 | Not applicable |
| Number of characterized genomic co-alterations (excludes VUSs) (median, IQR) (GNA† alterations excluded from the counts) | 3 (2 to 6) | 3 (2 to 5) | 5 (2 to 8) | 0.0028 | Not applicable |
| Tumor mutational burden (TMB) (median, IQR) (includes VUSs) | 4 (2 to 6.75) | 4 (2 to 6) | 4 (1.75 to 7) | 0.83 | |
| Tumor mutational burden (TMB): Count of “High” (>20 mutations/mb) | 73 (6.9%) (73/1062) |
71 (7.0%) (71/1010) |
2 (3.8%) (2/52) |
0.57 | |
| Additional alterations | |||||
| TP53 | 543 (40.3%) | 526 (40.7%) | 17 (30.9%) | 0.16 | |
| KRAS | 202 (15.0%) | 185 (14.3%) | 17 (30.9%) | 0.0029 | 2.7 (1.4 to 5.0) |
| MYC | 119 (8.8%) | 108 (8.4%) | 11 (20.0%) | 0.0067 | 2.8 (1.2 to 5.6) |
| AURKA | 20 (1.5%) | 13 (1.0%) | 7 (12.7%) | 6.58–6 | 14.3 (4.6 to 40.6) |
| CDKN2A | 210 (15.6%) | 204 (15.8%) | 6 (10.9%) | 0.45 | |
| ARID1A | 68 (5.0%) | 63 (4.9%) | 5 (9.1%) | 0.19 | |
| SMAD4 | 59 (4.4%) | 54 (4.2%) | 5 (9.1%) | 0.088 | |
| EGFR | 115 (8.5%) | 111 (8.9%) | 4 (7.3%) | 0.99 | |
| APC | 106 (7.9%) | 102 (7.9%) | 4 (7.3%) | 0.99 | |
| CDKN2A/B | 117 (8.7%) | 113 (8.7%) | 4 (7.3%) | 0.99 | |
| CCND1 | 64 (4.7%) | 60 (4.6%) | 4 (7.3%) | 0.33 | |
| FGF3 | 53 (3.9%) | 49 (3.8%) | 4 (7.3%) | 0.27 | |
| FGF19 | 53 (3.9%) | 49 (3.8%) | 4 (7.3%) | 0.27 | |
| FGF4 | 52 (3.9%) | 48 (3.7%) | 4 (7.3%) | 0.16 | |
| MCL1 | 40 (3.0%) | 36 (2.8%) | 4 (7.3%) | 0.076 | |
| SRC | 9 (0.67%) | 5 (0.39%) | 4 (7.3%) | 0.00027 | 20.1 (3.9 to 96.1) |
| TOP1 | 8 (0.59%) | 4 (0.31%) | 4 (7.3%) | 0.00015 | 25.1 (4.5 to 138.5) |
| PIK3CA | 138 (10.2%) | 135 (10.4%) | 3 (5.5%) | 0.36 | |
| NF1 | 77 (5.7%) | 74 (5.7%) | 3 (5.5%) | 0.99 | |
| ERBB2 | 59 (4.4%) | 56 (4.3%) | 3 (5.5%) | 0.73 | |
| TERT | 88 (6.5%) | 85 (6.6%) | 3 (5.5%) | 0.99 | |
| BRCA2 | 48 (3.6%) | 45(3.5%) | 3 (5.5%) | 0.44 | |
| PDGFRA | 29 (2.2%) | 26 (2.0%) | 3 (5.5%) | 0.11 | |
| DNMT3A | 36 (2.7%) | 33 (2.6%) | 3 (5.5%) | 0.18 | |
| CCNE1 | 25 (1.9%) | 22 (1.7%) | 3 (5.5%) | 0.078 | |
| AKT2 | 16 (1.2%) | 13 (1.0%) | 3 (5.5%) | 0.025 | 5.7 (1.0 to 21.5) |
| CBL | 8 (0.59%) | 5 (0.39%) | 3 (5.5%) | 0.0031 | 14.8 (2.2 to 78.2) |
| LYN | 4 (0.30%) | 1 (0.078%) | 3 (5.5%) | 0.00025 | 73.4 (5.8 to 3802.0) |
| ZNF703 | 24 (1.8%) | 21 (1.6%) | 3 (5.5%) | 0.071 | |
| PTEN | 100 (7.4%) | 98 (7.6%) | 2 (3.6%) | 0.43 | |
| MET | 38 (2.8%) | 36 (2.8%) | 2 (3.6%) | 0.67 | |
| MLL2 | 50 (3.7%) | 48 (3.7%) | 2 (3.6%) | 0.99 | |
| BRAF | 89 (6.6%) | 88 (6.8%) | 1 (1.8%) | 0.26 | |
| NOTCH1 | 51 (3.8%) | 50 (3.9%) | 1 (1.8%) | 0.72 | |
| RB1 | 59 (4.4%) | 58 (4.5%) | 1 (1.8%) | 0.51 |
*
Unless otherwise stated, aberrations refer to characterized alterations. “GNA†” refers to GNAS, GNAQ or GNA11 aberrations.
**
For comparing continuous values, the Wilcoxon rank-sum test was used; for comparing frequencies, the two-sided Fisher’s exact test was used. Bolded text indicates statistical significance at the alpha = 0.05 level.
Abbreviations: CI = confidence interval; VUS = variant of unknown significance.