Table 1.
Performance assessment of INT2GRATE in LS-related colorectal cancer.
| Subjects | PREMM score | Germline alteration | MLH1 hypermethylation | MSI | IHC | INT2GRATE Code ID |
|---|---|---|---|---|---|---|
| Inactivating somatic allele | ||||||
| 30 | 5.90% | MSH2:EX12_15del | Neg | MSI-High | loss of MSH2 and MSH6 | IV-I |
| MSH2:c.1697dupA (p.N566Kfs*2) | ||||||
| 31 | 6.70% | MSH2:c.226C>T (p.Q76*) | Neg | MSI-High | loss of MSH2 and MSH6 | IV-I |
| MSH2:c.2334C>A (p.C778*) | ||||||
| 32 | 4.20% | MSH6:c.3436C>T (p.Q1146*) | Neg | MSI-High | loss of MSH6 | V-I |
| MSH6:c.3238_3239delCT (p.L1080Vfs*12) | ||||||
| 33 | 3.00% | MSH6:c.3416G>T (p.G1139V) | Neg | MSI-High | loss of MSH6 | V-I |
| MSH6:c.3261delC (p.F1088Sfs*2) | ||||||
| 34 | 2.50% | MSH6:c.3984_3987dupGTCA (p.L1330Vfs*12) | Neg | MSI-High | loss of MSH6 | V-I |
| MSH6:c.2933delA (p.Q978Rfs*19) | ||||||
| 35 | 4.00% | PMS2:c.736_741delCCCCCTins11 (p.P246Cfs*3) | Neg | MSI-High | loss of PMS2 | III-I |
|
PMS2 c.1376_1405del30 (p.S459*) | ||||||
| 36 | 2.90% | PMS2:c.2192_2196del (p.L731Cfs*3) | Neg | MSI-High | loss of PMS2 | III-I |
| PMS2 one copy loss | ||||||
| 37 | 7.00% | MSH2:c.309T>A (p.Y103*) | Neg | MSI-High | loss of MSH2 and equivocal MSH6** | IHC pattern not included in INT2GRATE assessment for VUS |
| MSH2 single copy loss | ||||||
| 38 | 2.00% | PMS2:c.2117delA (p.K706Sfs*19) | Positive | MSI-High | loss of MLH1 and PMS2 | I-II, I-III, or I-IV |
| None Detected | ||||||
| 39 | 5.40% | PMS2:c.767delG ( p.G256Vfs*2) | Neg | MSI-High | loss of PMS2 and MSH6 | I-IV |
| None Detected | ||||||
| 40 | 2.4% | MSH6:c.3261dupC (p.F1088Lfs*5) | Neg | MSI-High | loss of MSH6 | I-II or I-IV |
| None Detected | ||||||
| 41 | 5.60% | MSH6:c.3261delC (p.F1088Sfs*2) | Neg | MSI-High | loss of MSH6 | I-IV |
| None Detected | ||||||
| 42 | 6.20% | MSH6:c.3939_3957dup19 (p.A1320Sfs*5) | Neg | MSI-High | loss of MSH6 | I-IV |
| None Detected | ||||||
| 43 | 4.70% | PMS2:c.137G>T (p.S46I) | Neg | MSI-S | loss of PMS2 | I-IV or I-V |
| None Detected | ||||||
| 44 | 2.70% | MSH6:c.10C>T (p.Q4*) | N/A | MSI-High | Loss of MSH6 | I-IV |
| None Detected | ||||||
| 45 | 3.30% |
PMS2:c.861_864delACAG (p.R287Sfs*19) |
Neg | MSI-High | loss of PMS2 | I-IV |
| PMS2:c.404T>C (p.L135P) | ||||||
| 46 | 3.10% | PMS2:c.137G>T (p.S46I) | Neg | MSI-High | loss of PMS2 | I-IV |
| PMS2:c.163+5G>A | ||||||
| 47 | 14.80% | MSH2:c.2152C>T (p.Q718*) | Neg | MSI-High | loss of MSH2 and MSH6 | I-IV |
| MSH2:c.1241_1255del15 (p.L414_I418del) | ||||||
| 48 | 2.00% | PMS2:EX9_10del | Neg | MSI-High | loss of PMS2 | I-II |
| PMS2 single copy loss | ||||||
| 49 | 2.4% | MSH6:c.3268_3274delGAGCTTA (p.E1090Kfs*23) | N/A | MSI-High | Loss of MSH6 | I-II |
| MSH6:c.3731T>G (p.L1244*) | ||||||
| 50 | 7.00% | MSH6:c.10C>T (p.Q4*) | Neg | None | loss of MSH6 | I-V |
| MSH6:c.2386G>T (p.E796*) | ||||||
| 51 | 5.70% | MSH2:c.1906G>C (p.A636P) | Neg | None | loss of MSH2 and MSH6 | I-V |
| MSH2:c.1861C>T (p.R621*) | ||||||
| 52 | 5.10% | MSH6:c.742C>T (p.R248*) | Neg | MSI-S | loss of MSH6 | I-V |
| MSH6:c.3261delC (p.F1088Sfs*2) |
IHC, Immunohistochemistry; LOH, Loss of heterozygosity; MMR, Mismatch repair; MMR-D, Mismatch repair-deficient; MMR-P, Mismatch repair-proficient; MSI, Microsatellite instability; MSI-H, Microsatellite instable-high.
**Partial or equivocal IHC pattern not incorporated in INT2GRATE assessment.