Table 1.
Molecular and genetic data of our institutional cases with double somatic mismatch repair gene mutation/alteration.
| Case ID | Tumor mutation burden (mutations/megabase) |
Genes mutated† | Mutation 1† | Mutation 2† | Mutation 3† | Alteration 4† | Loss of hetero-zygosity (copy neutral) | Microsatellite instability-high (by MSIsensor) | Mismatch repair protein lost by immuno-histochemistry | Integrated Genetic Interpretation |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 49.8 | MSH2 | R621* | V100I | K21Efs*20 | MLH1 methylation | Detected | MSH2/MSH6/ MLH1/PMS2 |
Double MSH2 likely pathogenic mutations AND MLH1 promoter hypermethylation | |
| 2 | 89.5 | MSH2 | R534H | E881* | M663_H665del | Detected | MSH2/MSH6 | Double MSH2 likely pathogenic mutations | ||
| 3 | 55.1 | MSH2 | P622Q | Q158* | Detected | MSH2/MSH6 | Double MSH2 likely pathogenic mutations | |||
| 4 | 64.9 | MSH2 | E56* | S743* | Detected | MSH2/MSH6 | Double MSH2 likely pathogenic mutations | |||
| 5 | 74.8 | MSH2 | E48fs | T234fs | MSH2/MSH6 | Double MSH2 likely pathogenic mutations | ||||
| 6 | 84.6 | MSH2, MSH6 | R406* (MSH2) | R680* (MSH2) | F1088fs (MSH6) | Detected | MSH2/MSH6 | Double MSH2 likely pathogenic mutations, single MSH6 likely pathogenic mutation | ||
| 7 | 330.6 | MSH6 | R577H | E641* | Q1048R | E1322* | Detected | MSH6 | Three MSH6 likely pathogenic mutations | |
| 8 | 67.9 | MSH6 | D439G | R922* | Detected | MSH6 | Double MSH6 likely pathogenic mutations | |||
| 9 | 88.5 | MLH1, MSH6 | K361* (MLH1) | R462I (MLH1) | K195* (MLH1) | G650D (MSH6) | Detected | MLH1/PMS2 | Double MLH1 likely pathogenic mutations, single MSH6 variant of unknown significance | |
| 10 | 55.1 | MLH1, MSH6 | M35del (MLH1) | E414fs (MLH1) | F1088fs (MSH6) | Detected | MLH1/PMS2 | Double MLH1 likely pathogenic mutations, single MSH6 likely pathogenic mutation | ||
| 11 | 33.5 | MLH1 MSH6 |
T117M | F1088Lfs*5 (msh6) | Detected | Detected | MLH1/PMS2 | MLH1 likely pathogenic mutation+ loss of heterozygosity, single MSH6 likely pathogenic mutation | ||
| 12 | 66.9 | MLH1 | T278Nfs*29 | Detected | Detected | MLH1/PMS2 | MLH1 likely pathogenic mutation+ loss of heterozygosity | |||
| 13 | 47.2 | MSH2 | L310R | Detected | Detected | MSH2/MSH6 | MSH2 likely pathogenic mutation + loss of heterozygosity | |||
| 14 | 36.4 | MLH1 | X182_splice | Detected | Detected | MLH1/PMS2 | MLH1 likely pathogenic mutation + loss of heterozygosity | |||
| 15 | 61.0 | MSH2 | Q518fs | Detected | Detected | MSH2/MSH6 | MSH2 likely pathogenic mutation + loss of heterozygosity |
†
Refers to mismatch repair genes mutated/altered somatically, and mutations are displayed by amino acid alteration;
* -
truncating nonsense mutation, fs - frame shift, del – deletion; Bolded mutations are pathogenic or likely pathogenic.