Table 1. Overview of patients with a POLE/POLD1-EDM mutated tumor.
| Patient | IHC-negative staining | MSI | Age of onset | Family history | Number of variants | Gene | Variant | Amino acid alteration | % |
|---|---|---|---|---|---|---|---|---|---|
| Somatic POLE/POLD1-EDM variant | |||||||||
| sLS-05 | None | L | 62 | FDR | 330 | POLE | c.1367C>T | p.(A456V) | 28% |
| MLH1 | LOH | ||||||||
| PMS2 | LOH | ||||||||
| sLS-07 | MSH6 (1) | S | 39 | TDR | 37 | POLE | c.1231G>T | p.(V411L) | 44% |
| MSH6 | c.2735G>A | p.(W912*) | 10% | ||||||
| MSH6 | c.2876 G>A | p.(R959H) | 14% | ||||||
| sLS-09 | MSH6 (2) | L | 42 | FDR | 16 | POLE | c.857C>G | p.(P286R) | 38% |
| MSH6 | c.2539G>T | p.(E847*) | 36% | ||||||
| MSH2 | c.1166G>A | P.(R389Q) | 38% | ||||||
| sLS-19 | PMS2 | H | 45 | FDR | 221 | POLE | c.1376C>T | p.(S459F) | 21% |
| POLE | c.856C>T | p.(P286S) | 9% | ||||||
| MLH1 | c.199G>A | p.(G67R) | 19% | ||||||
| MLH1 | LOH | ||||||||
| PMS2 | c.308C>T | p.(T103I) | 11% | ||||||
| PMS2 | LOH | ||||||||
| sLS-24 | None | L | 34 | FDR | 115 | POLE | c.1366G>C | p.(A456P) | 28% |
| sLS-66 | MSH6 | L | 66 | SDR | 25 | POLD1 | c.1433G>A | p.(S478N) | 32% |
| MSH6 | c.3600_3601del | p.(L1201Hfs*13) | 28% | ||||||
| sLS-80 | MSH2/MSH6 | H | 52 | FDR | 5 | POLD1 | c.1429G>A | p.(V477M) | 26% |
| MSH6 | c.3961A>G** | p.(R1321G) | 52% | ||||||
| MSH6 | c.3186C>A | p.(C1062*) | 25% | ||||||
| sLS-87 | MSH2/MSH6 | H | 49 | FDR | 9 | POLE | c.1218C>G | p.(N406E) | 16% |
| MSH6 | c.3473_3475del** | p.(C1158del) | 53% | ||||||
| MSH6 | c.3311_3312delTT | p.(F1104Trpfs*3) | 21% | ||||||
| sLS-101 | PMS2 | H | 55 | FDR | 5 | POLD1 | c.1003A>G | p.(I335V) | 22% |
| PMS2 | c.1687C>T | p.(R563*) | 30% | ||||||
| sLS-105 | MLH1/ PMS2 | H | 49 | No | 184 | POLE | c.846_847delinsTT | p.(L283F) | 13% |
| MLH1 | c.1614G>A | p.(W538*) | 13% | ||||||
| Germline POLE/POLD1-EDM variant | |||||||||
| sLS-16 | None (3) | L | 41 | FDR | 185 | POLD1 | c.961G>A | p.(G321S) | 55% |
| sLS-67 | MLH1/ PMS2 | H | 53 | SDR | 91 | POLE | c.861T>A | p.(D287E) | 50% |
| MLH1 | c.208-1G>A | p.? | 14% | ||||||
| MLH1 | c.440_447del | p.(G147Dfs*22) | 19% | ||||||
Abbreviation: EDM, exonuclease domain.
IHC was performed for MLH1, MSH2, MSH6 and PMS2. Numbers behind staining results indicate: (1) at least MSH6 negative, (2) PMS2 not tested and (3) inconclusive testing. MSI status is defined as MSI-H (H), MSI-L (L) or MSS (S). Age of onset is the age at which the first Lynch-associated tumor occurred. All patients presented with colorectal cancer, except patients sLS-87 and sLS-101 who presented with endometrial cancer. Number of variants depicts the number of somatic variants with a frequency >10% identified in the sequenced region of 31 kb. Stop codons are indicated with an asterisk (*). Germline variants of unknown significance (VUS) are indicated with a double asterisk (**). % shows the percentage of variant reads. Family history is defined as a first-degree relative with LS-associated tumors (FDR), second-degree relative with LS-associated tumors (SDR), third-degree relative with LS-associated tumors (TDR) or no LS in the family (No).