Table 2.
A comparison of subgroups of homo/heterozygous mutation occurrence (HO/HE) and occurrence of mutations resulting in modified protein or lack of protein (MS/NS) in human cancer cell lines and surgical samples
| Group | Gene | Number of samples | %MS-HE | %MS-HO | %NS-HE | %NS-HO | MS-HE//NS-HO | NS-HE//NS-HO | MS-HE//MS-HO | MS-HE//NS-HE | MS-HO//NS-HO | MS-HO//NS-HE | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Classical 2 hits | TP53 | TS | 401 | 43.9 | 36.2 | 10.2 | 9.7 | p < 0.001 | p < 0.001 | p < 0.001 | p > 0.1 | p > 0.1 | p < 0.001 |
| CL | 566 | 9.2 | 68.9 | 2.5 | 19.4 | ||||||||
| RB1 | TS | 47 | 10.6 | 21.3 | 34.0 | 34.0 | p = 0.003 | p < 0.001 | p = 0.007 | p > 0.1 | p > 0.1 | p < 0.001 | |
| CL | 102 | 1.0 | 33.3 | 2.0 | 63.7 | ||||||||
| NF1 | TS | 96 | 22.9 | 14.6 | 32.3 | 30.2 | p > 0.1 | p = 0.013 | p = 0.007 | p > 0.1 | p = 0.098 | p < 0.001 | |
| CL | 40 | 12.5 | 42.5 | 7.5 | 37.5 | ||||||||
| NOTCH1 | TS | 326 | 46.9 | 2.5 | 50.0 | 0.6 | p < 0.001 | p < 0.001 | p < 0.001 | p > 0.1 | p = 0.141 | p < 0.001 | |
| CL | 67 | 34.3 | 2.5 | 29.9 | 17.9 | ||||||||
| PTEN | TS | 270 | 23.0 | 20.7 | 24.8 | 31.5 | p < 0.001 | p < 0.001 | p < 0.001 | p > 0.1 | p > 0.1 | p < 0.001 | |
| CL | 184 | 4.3 | 37.0 | 3.3 | 55.4 | ||||||||
| 3 hits | BRCA2 | TS | 17 | 35.3 | 17.6 | 11.8 | 35.3 | p = 0.042 | p < 0.001 | p = 0.028 | p > 0.1 | p = 0.047 | p > 0.1 |
| CL | 17 | 0.0 | 35.3 | 17.6 | 47.1 | ||||||||
| SMAD4 | TS | 173 | 12.7 | 52.6 | 9.8 | 24.9 | p < 0.001 | p = 0.091 | p = 0.033 | p > 0.1 | p = 0.003 | p > 0.1 | |
| CL | 105 | 2.9 | 43.8 | 4.8 | 48.6 | ||||||||
| SOCS1 | TS | 18 | 55.6 | 22.2 | 22.2 | 0.0 | p = 0.003 | p = 0.061 | p = 0.074 | p > 0.1 | p > 0.1 | p > 0.1 | |
| CL | 15 | 13.3 | 40.0 | 13.3 | 33.3 | ||||||||
| STK11 | TS | 87 | 36.8 | 24.1 | 20.7 | 18.4 | p < 0.001 | p < 0.001 | p = 0.002 | p > 0.1 | p = 0.005 | p = 0.005 | |
| CL | 61 | 4.9 | 24.6 | 1.6 | 68.9 | ||||||||
| MSH6 | TS | 26 | 53.8 | 11.5 | 30.8 | 3.8 | p < 0.001 | p < 0.001 | p = 0.002 | p > 0.1 | p > 0.1 | p = 0.004 | |
| CL | 20 | 5.0 | 35.0 | 0.0 | 60.0 | ||||||||
| SMARCA4 | TS | 13 | 38.5 | 46.2 | 7.7 | 7.7 | p = 0.063 | p > 0.1 | p > 0.1 | p > 0.1 | p = 0.040 | p > 0.1 | |
| CL | 44 | 22.7 | 29.5 | 2.3 | 45.5 | ||||||||
| APC | TS | 199 | 8.5 | 9.5 | 27.6 | 54.3 | p = 0.126 | p < 0.001 | p > 0.1 | p > 0.1 | p = 0.025 | p > 0.1 | |
| CL | 65 | 4.6 | 3.1 | 9.2 | 83.1 | ||||||||
| CDKN2A | TS | 1,813 | 3.6 | 61.7 | 1.8 | 32.8 | p < 0.001 | p < 0.001 | p < 0.001 | p > 0.1 | p < 0.001 | p < 0.001 | |
| CL | 9,900 | 0.3 | 46.6 | 0.1 | 53.0 | ||||||||
| 3 hits/final stage | BAP1 | TS | 32 | 3.1 | 40.6 | 6.3 | 50.0 | p > 0.1 | p = 0.019 | p > 0.1 | p > 0.1 | p > 0.1 | p = 0.054 |
| CL | 9 | 0.0 | 33.3 | 44.4 | 22.2 | ||||||||
| FAM123B | TS | 97 | 2.1 | 37.1 | 14.4 | 46.4 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | |
| CL | 7 | 14.3 | 14.3 | 0.0 | 71.4 | ||||||||
| NF2 | TS | 247 | 2.8 | 17.0 | 0.8 | 79.4 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p = 0.001 | p > 0.1 | |
| CL | 25 | 4.0 | 32.0 | 0.0 | 64.0 | ||||||||
| SMARCB1 | TS | 179 | 0.6 | 16.2 | 0.6 | 82.7 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | |
| CL | 20 | 5.0 | 15.0 | 0.0 | 80.0 | ||||||||
| VHL | TS | 415 | 4.6 | 39.0 | 2.9 | 53.5 | p = 0.091 | p = 0.036 | p > 0.1 | p > 0.1 | p > 0.1 | 0.073 | |
| CL | 26 | 11.5 | 38.5 | 11.5 | 38.5 | ||||||||
| 3 hits/small group | CDH10 | TS | 6 | 83.3 | 16.7 | 0.0 | 0.0 | p > 0.1 | N/A | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 |
| CL | 7 | 28.6 | 28.6 | 14.3 | 28.6 | ||||||||
| MLH1 | TS | 9 | 44.4 | 22.2 | 0.0 | 33.3 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | |
| CL | 13 | 15.4 | 23.1 | 0.0 | 61.5 | ||||||||
| MSH2 | TS | 9 | 44.4 | 0.0 | 33.3 | 22.2 | p > 0.1 | p > 0.1 | p = 0.076 | p > 0.1 | p > 0.1 | p = 0.004 | |
| CL | 15 | 13.3 | 26.7 | 13.3 | 46.7 | ||||||||
| SETD2 | TS | 5 | 40.0 | 40.0 | 0.0 | 20.0 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | p > 0.1 | |
| CL | 10 | 20.0 | 30.0 | 10.0 | 40.0 | ||||||||
| Oncogene | EGFR | TS | 768 | 81.6 | 17.8 | 0.3 | 0.3 | p > 0.1 | N/A | p > 0.1 | N/A | N/A | N/A |
| CL | 26 | 84.6 | 15.4 | 0.0 | 0.0 | ||||||||
| KIT | TS | 846 | 77.3 | 21.9 | 0.8 | 0.0 | p > 0.1 | N/A | p > 0.1 | N/A | N/A | N/A | |
| CL | 13 | 61.5 | 38.5 | 0.0 | 0.0 | ||||||||
| KRAS | TS | 1,601 | 58.5 | 41.3 | 0.1 | 0.0 | p > 0.1 | N/A | p > 0.1 | N/A | N/A | N/A | |
| CL | 177 | 58.8 | 41.2 | 0.0 | 0.0 | ||||||||
Classical 2 hits, the genes which followed the 2-hit pattern; 3 hits, the genes which followed the 3-hit pattern; 3 hits/final stage, the genes which may have followed the 3-hit pattern, but the proportion of homozygous nonsense mutations is very high in tumors; 3 hits/small group, the genes which may have followed the 3-hit pattern, but the groups were not numerous enough to verify that
TS tumor sample, CL cell line, MS mutation resulting in modified protein, NS mutation resulting in lack of protein, HO homozygous mutation, HE heterozygous mutation