Table 1. Mutations and MAF in patients with TKI resistant tumors.
| Casea | EGFR TKI-sensitizing | EGFR T790Mb | PIK3CAc,d,e | Other mutationsc,d,e | mut no.f |
|---|---|---|---|---|---|
| 1 | E746_A750del (43%) | 13% | 1 | ||
| 2 | L858R (17%) | 1.1%b | 1 | ||
| 3A | E746_A750del (57%) | 16% | V344G (13%)d | 2 | |
| 3B | E746_A750del (39%) | 13% | V344G (16%)d | 2 | |
| 3C | E746_A750del (66%) | 27% | V344G (25%)d | 2 | |
| 4A | A763_Y764insFQEA (35%) | 9.6% | G1049R (73%)e | 2 | |
| 4C | A763_Y764insFQEA (8.2%) | 2.1% | G1049R (30%)e | 2 | |
| 5 | E746_A750del (32%) | 8.3% | E453K (16%)c | 2 | |
| 6 | E746_A750del (26%) | 5.8% | 1 | ||
| 7 | L858R (74%) | 31% | 1 | ||
| 8 | E746_A750del (47%) | 11% | 1 | ||
| 9 | L858R (8.6%) | 6.1% | H1047L (6.9%)c | EGFR/K860I (8.5%)c | 2 |
| 10 | L747_A750delinsP (36%) | 3.6% | E542K (6.1%)d | EGFR/S768_V769delinsIL (12%)d | 3 |
| 11a | L858R (54%) | negative (432) | 0 | ||
| 12 | E746_A750del (52%) | 22% | 1 | ||
| 13 | E746_A750del (68%) | negative (618) | 0 | ||
| 14 | L858R (11%) | negative (329) | 0 | ||
| 15 | E746_S752delinsIV(36%) | negative (291) | EGFR/G724S (47%)e | 0 | |
| 17 | G719C (46%) | 17% | EGFR/S768I (45%)e | 1 | |
| 18 | L747_S752del (22%) | 3.1% | 1 | ||
| 19B | E746_A750del (9.2%) | 2.0% | 1 | ||
| 19Ca | E746_A750del (64%) | negative (680) | 0 | ||
| 21 | E746_A750del (57%) | 16% | 1 | ||
| 22 | E746_A750del (77%) | 20% | 1 | ||
| 23 | E746_A750del (63%) | 42% | 1 | ||
| 24B | E746_T751delinsA (33%) | 12% | Y1021C (16%)c | EGFR/K754Q (33%)e | 2 |
| 25 | E746_A750del (56%) | 14% | 1 | ||
| 26 | E746_A750del (84%) | negative (494) | 0 | ||
| 27 | L858R (46%) | 26% | 1 | ||
| 28 | L858R (34%) | 4.3% | E110del (20%)c | KRAS/G12C (33%)d | 3 |
| 29a | L747_P753delinsS (62%) | negative (2437) | E545K (23%)c | 1 | |
| 30 | L747_T751delinP (32%) | 14% | H1047R (21%)c | 2 | |
| 31 | L747_P753delinsQ (29%) | 10% | 1 | ||
| 32 | E746_A750del (65%) | 33% | 1 | ||
| 33 | E746_A750del (47%) | 4.1% | 1 | ||
| 34 | E746_S752delinsV (67%) | 37% | 1 | ||
| 35 | L747_P755delinsSKG (9.4%) | negative (740) | E545K (8.3%)d | 1 | |
| 36 | L858R (12%) | 8.7% | EGFR/E709K (17%)e | 1 | |
| 37 | L747_P753delinsS (91%) | 5.0% | 1 | ||
| 38 | E709_T710delinsD (48%) | negative (2214) | 0 | ||
| 39 | E746_A750del (36%) | 8.9% | 1 | ||
| 40 | L858R (43%) | 13% | 1 | ||
| 41 | L858R (52%) | 9.1% | 1 |
Small cell carcinoma. Others: adenocarcinoma.
Number in parentheses indicates depth of coverage for specimens with negative p.T790M mutation. The depth of coverage was more than 150 reads for all p.T790M positive cases. Retrospective NGS assays of 3 subareas from the pleural biopsy of specimen 2 showed 0.7% (1399 reads), 2.6% (1185 reads) and 2.6% (992 reads) p.T790M, respectively.
The presence or absence of mutation in pre-treatment specimens was not known.
Mutations were not present in the pre-treatment specimens. Pre-treatment specimens of patients 3 and 4 were examined retrospectively by NGS.
Mutations were present in the pre-treatment specimens.
mut no.: The total number of resistance mutations in each patient's samples, including the EGFR 790M mutation, the EGFR p.S768_V769delinsIL mutation of specimen 10 (not present in the pre-treatment specimens), PIK3CA mutations, and the KRAS p.G12C mutation of specimen 28. The original TKI-sensitizing mutations and co-existing EGFR mutations in the pre-treatment specimens of patients 15, 17, 24 and the EGFR p.K860I mutation of specimen 9 were not included.