Table 1.
Clinico-pathologic characteristics of patients with four major KRAS mutated tumors by KRAS mutation subtype.
| CRC (N = 23,797 KRAS mutated cases) | ||||||||
|---|---|---|---|---|---|---|---|---|
| KRAS G12C | KRAS G12D | KRAS G12V | KRAS G13D | KRAS WT | KRAS non-G12C | G12C vs non-G12C | G12C vs. WT | |
| # cases | 1739 | 7312 | 5026 | 3963 | 24,640 | 22,058 | – | – |
| Median age (range) | 60 (22–89+) | 60 (18–89+) | 61 (20–89+) | 61 (19–89+) | 60 (18–89+) | 60 (18–89+) | 0.21 | 0.27 |
| ≥65 years old | 35% (608) | 38% (2761) | 38% (1902) | 38% (1518) | 37% (9194) | 38% (8349) | 0.04 | 0.10 |
| Sex M:F % | 52:48 | 53:47 | 53:47 | 53:47 | 57:43 | 53:47 | 0.78 | P < 0.001 |
| Median TMB (range) | 3.8 (0–90) | 3.8 (0–219) | 3.5 (0–373) | 3.8 (0–608) | 3.8 (0–865) | 3.8 (0–608) | 0.59 | 0.07 |
| TMB ≥ 10 mutations/Mb (n) | 4.7% (81) | 6.6% (482) | 3.2% (163) | 9.5% (377) | 11% (2670) | 6.8% (1510) | 0.002 | P < 0.001 |
| MSI-H % (n) | 0.65% (11/1691) | 3.4% (237/7048) | 0.57% (28/4870) | 5.6% (217/3860) | 7.5% (1784/23,929) | 3.2% (690/21,347) | P < 0.001 | P < 0.001 |
| PD-L1 1–49% | 15% (68/445) | 17% (315/1832) | 13% (173/1282) | 16% (166/1022) | 13% (836/6552) | 16% (880/5595) | 0.92 | 0.21 |
| PD-L1 ≥ 50% | 1.6% (7/445) | 1.4% (26/1832) | 0.47% (6/1282) | 1.2% (12/1022) | 2.0% (134/6552) | 1.0% (58/5595) | 0.50 | 0.72 |
| Non-Sq NSCLC (N = 21,866 KRAS mutated cases) | ||||||||
|---|---|---|---|---|---|---|---|---|
| KRAS G12C | KRAS G12D | KRAS G12V | KRAS G12A | KRAS WT | KRAS non-G12C | G12C vs non-G12C | G12C vs. WT | |
| # cases | 8790 | 3085 | 4197 | 1548 | 40,042 | 13,076 | – | – |
| Median age (range) | 67 (24–89+) | 69 (23–89+) | 68 (24–89+) | 69 (30–89+) | 67 (18–89+) | 68 (23–89+) | P < 0.001 | P < 0.001 |
| ≥65 years old | 60% (5282) | 64% (1986) | 62% (2584) | 65% (1000) | 59% (23,651) | 62% (8130) | 0.003 | 0.08 |
| Sex M:F % | 40:60 | 44:56 | 42:58 | 42:58 | 49:51 | 43:57 | P < 0.001 | P < 0.001 |
| Median TMB (range) | 7.8 (0–104) | 5.0 (0–164) | 6.3 (0–937) | 6.3 (0–68) | 5.2 (0–1765) | 6.3 (0–1255) | P < 0.001 | P < 0.001 |
| TMB ≥ 10 mutations/Mb (n) | 40% (3546) | 24% (754) | 34% (1412) | 31% (485) | 32% (12,842) | 33% (4260) | P < 0.001 | P < 0.001 |
| MSI-H % (n) | 0.20% (17/8473) | 0.30% (9/2974) | 0.20% (8/4054) | 0.13% (2/1491) | 0.35% (136/38,548) | 0.26% (33/12,605) | 0.59 | 0.03 |
| PD-L1 1–49% | 28% (1067/3879) | 29% (377/1285) | 28% (506/1820) | 29% (189/655) | 30% (4937/16,351) | 28% (1578/5633) | 0.72 | 0.001 |
| PD-L1 ≥ 50% | 44% (1690/3879) | 37% (477/1285) | 39% (705/1820) | 37% (244/655) | 29% (4769/16,351) | 38% (2147/5633) | P < 0.001 | P < 0.001 |
| PDAC (N = 17,817 KRAS mutated cases) | ||||||||
|---|---|---|---|---|---|---|---|---|
| KRAS G12C | KRAS G12D | KRAS G12V | KRAS G12R | KRAS WT | KRAS non-G12C | G12C vs non-G12C | G12C vs. WT | |
| # cases | 300 | 7654 | 5542 | 2825 | 1536 | 17,517 | – | – |
| Median age (range) | 67 (37–87) | 66 (21–89+) | 66 (28–89+) | 66 (29–89+) | 64 (23–89+) | 66 (21–89+) | 0.42 | P < 0.001 |
| ≥65 years old | 59% (176) | 56% (4253) | 55% (3065) | 59% (1668) | 49% (757) | 56% (9888) | 0.64 | 0.02 |
| Sex M:F % | 59:41 | 53:47 | 52:48 | 49:51 | 59:41 | 52:48 | 0.06 | 0.95 |
| Median TMB (range) | 1.7 (0–21) | 1.3 (0–344) | 1.3 (0–166) | 1.3 (0–211) | 1.7 (0–6906) | 1.3 (0–355) | 0.001 | 0.55 |
| TMB ≥ 10 mutations/Mb (n) | 2.0% (6) | 1.0% (78) | 0.79% (44) | 0.85% (24) | 5.5% (85) | 1.0% (177) | 0.32 | 0.03 |
| MSI-H % (n) | 0.34% (1/292) | 0.37% (28/7472) | 0.20% (11/5387) | 0.15% (4/2759) | 1.5% (23/1487) | 0.32% (55/17,065) | 0.74 | 0.37 |
| PD-L1 1%-49% | 35% (29/84) | 33% (706/2118) | 30% (457/1528) | 25% (187/755) | 24% (98/410) | 31% (1484/4821) | 0.64 | 0.16 |
| PD-L1 ≥50% | 2.4% (2/84) | 7.7% (164/2118) | 4.6% (71/1528) | 6.0% (45/755) | 6.6% (27/410) | 6.3% (302/4821) | 0.35 | 0.37 |
| Endometrial (N = 2504 KRAS mutated cases) | ||||||||
|---|---|---|---|---|---|---|---|---|
| KRAS G12C | KRAS G12D | KRAS G12V | KRAS G12A | KRAS WT | KRAS non-G12C | G12C vs non-G12C | G12C vs. WT | |
| # cases | 175 | 771 | 657 | 291 | 11,639 | 2329 | – | – |
| Median age (range) | 64 (35–89+) | 63 (27–89+) | 63 (24–89+) | 64 (33–89+) | 66 (23–89+) | 64 (24–89+) | 0.95 | 0.01 |
| ≥65 years old | 46% (81) | 44% (340) | 44% (286) | 49% (144) | 56% (6484) | 46% (1082) | 1.0 | 0.03 |
| Sex M:F % | 0.57:99 | 0:100 | 0:100 | 0:100 | 0:100 | 0:100 | 0.21 | 0.03 |
| Median TMB (range) | 3.8 (0–54) | 3.8 (0–509) | 2.6 (0–384) | 3.8 (0–393) | 2.6 (0–908) | 3.8 (0–733) | 0.95 | 0.01 |
| TMB ≥ 10 mutations/Mb (n) | 30% (52) | 34% (264) | 21% (141) | 31% (89) | 16% (1919) | 33% (759) | 0.78 | P < 0.001 |
| MSI-H % (n) | 26% (43/166) | 31% (225/718) | 19% (120/621) | 27% (72/270) | 13% (1459) | 29% (619) | 0.80 | P < 0.001 |
| PD-L1 1–49% | 39% (25/64) | 26% (66/258) | 24% (54/224) | 38% (39/104) | 28% (1135/4005) | 30% (245/814) | 0.32 | 0.09 |
| PD-L1 ≥50% | 4.7% (3/64) | 1.2% (3/258) | 1.3% (3/224) | 2.9% (3/104) | 1.8% (73/4005) | 2.0% (16/814) | 0.32 | 0.14 |
Ordinal relationships were examined using the Mann–Whitney U test; categorical relationships were examined using Fisher’s exact with correction for multiple comparisons. PD-L1 expression was only available for a subset of cases.
KRAS WT includes samples WT for KRAS mutations and amplifications.