TABLE 3.
Associations Between Common Mutations, Pathways, and Treatment Center
| Gene | All N = 81 No. (%) |
Chile N = 21 No. (%) |
Japan N = 11 No. (%) |
United States N = 49 No. (%) |
Unadjusted Pa | Adjusted Pa |
|---|---|---|---|---|---|---|
| Mutation burden (range)bb | 5 (0−27) | 7 (3−20) | 6 (1−23) | 4 (0−27) | <.001 | 0.006 |
| TP53 | 47 (58) | 16 (76.2) | 6 (54.5) | 25 (51) | .15 | 0.45 |
| SMAD4 | 25 (30.9) | 8 (38.1) | 4 (36.4) | 13 (26.5) | .58 | 0.68 |
| ARID1A | 20 (24.7) | 8 (38.1) | 0(0) | 12 (24.5) | .045 | 0.35 |
| ATM | 15 (18.5) | 3 (14.3) | 2 (18.2) | 10(20.4) | .92 | 0.92 |
| CDKN2A | 12 (14.8) | 4(19) | 2 (18.2) | 6 (12.2) | .60 | 0.68 |
| PIK3CA | 10 (12.3) | 3 (14.3) | 0(0) | 7(14.3) | .56 | 0.68 |
| TERT | 10 (12.3) | 3 (14.3) | 2 (18.2) | 5(10.2) | .70 | 0.75 |
| BRCA2 | 8 (9.9) | 2 (9.5) | 2 (18.2) | 4 (8.2) | .50 | 0.68 |
| KMT2D | 8 (9.9) | 4(19) | 1 (9.1) | 3 (6.1) | .21 | 0.45 |
| ERBB3 | 7 (8.6) | 0(0) | 1 (9.1) | 6 (12.2) | .24 | 0.45 |
| KRAS | 7 (8.6) | 4(19) | 1 (9.1) | 2 (4.1) | .09 | 0.35 |
| NF1 | 7 (8.6) | 4(19) | 1 (9.1) | 2 (4.1) | .09 | 0.35 |
| AR | 6 (7.4) | 3 (14.3) | 1 (9.1) | 2 (4.1) | .25 | 0.45 |
| ARID2 | 6 (7.4) | 0(0) | 1 (9.1) | 5 (10.2) | .32 | 0.51 |
| CDKN2B | 6 (7.4) | 3 (14.3) | 1 (9.1) | 2 (4.1) | .25 | 0.45 |
| All | Chile | Japan | United States | Unadjusted | Adjusted | |
| Pathway | (n = 81) | (n = 21) | (n = 11) | (n = 49) | p-value | p-value |
| Cell cycle | 23 (28.4) | 9 (42.9) | 3 (27.3) | 11 (22.4) | .18 | .62 |
| Chromatin Remodeling | 30 (37) | 11 (52.4) | 2 (18.2) | 17 (34.7) | .17 | .62 |
| NOTCH | 20 (24.7) | 8 (38.1) | 2 (18.2) | 10 (20.4) | .28 | .62 |
| NRF2 | 6 (7.4) | 1 (4.8) | 1 (9.1) | 4 (8.2) | >.95 | >.95 |
| p53 | 59 (72.8) | 18 (85.7) | 8 (72.7) | 33 (67.3) | .31 | .62 |
| PIK3 | 26 (32.1) | 9 (42.9) | 2 (18.2) | 15 (30.6) | .40 | .62 |
| RTK-RAS | 36 (44.4) | 11 (52.4) | 6 (54.5) | 19 (38.8) | .48 | .62 |
| TGF-β | 31 (38.3) | 10 (47.6) | 4 (36.4) | 17 (34.7) | .64 | .72 |
| WNT | 18 (22.2) | 4(19) | 4 (36.4) | 10 (20.4) | .44 | .62 |
Abbreviations: AR, androgen receptor; ARID1A, AT-rich interaction domain 1A; ARID2, AT-rich interaction domain 2; ATM, ATM serine/threonine kinase; CDKN2A, cyclin-dependent kinase inhibitor 2A; CDKN2B, cyclin-dependent kinase inhibitor 2b; ERBB3, Erb-B2 receptor tyrosine kinase 3; NF1, neurofibromin 1; NRF2, nuclear factor (erythraid-derived 2)-like 2; PIK3, phosphatidylinositide 3-kinases; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RTK-RAS, receptor tyrosine kinase-RAS, SMAD4, SMAD family member 4; TERT, telomerase reverse transcriptase; TGF-β, transforming growth factor β.
Bold type indicates statistical significance.
Mutation burden includes point mutations, copy number alterations (amplifications and deletions), and fusions.