Table 1.
Genetic and protein expression alterations of mismatch repair genes in Lynch syndrome (LS) and Lynch-like syndrome (LLS)
| ID | Germline MMR gene mutation |
Somatic mutation of MMR genes |
LOH at MMR genes |
MMR protein expressionb |
Race |
|---|---|---|---|---|---|
| LS: MMR germline mutations | |||||
| 1 | Del MSH2/EPCAM |
MLH1 rs267607751c MSH2 c.376delG (G126fs) |
None identified | MSH2 | WEA |
| 2 | MLH1 rs63750781c | NA | NA | MLH1/PMS2 | WEA |
| 3 | MSH6 c.1701delTT (K567fs) |
MSH2 c.G2272A (D758N), MSH6 rs587779246c |
None identified | MSH2/MSH6 | AA |
| 4 | PMS2 rs201451115c | MLH1 c.A560C (N187T) | PMS2 | PMS2 | WEA |
| 5a | MLH1 c.C1219T (Q407X) | NA | NA | MLH1/PMS2 | AA |
| LLS: No MMR germline mutations | |||||
| 6 | none identified | None identified | MLH1 | MSH2/MSH6 | AA |
| 7 | none identified | MLH1 rs63750781d | MLH1 | MLH1/PMS2 | WEA |
| 8 | none identified | MSH2 c.211-2T>G (2:47630543T>G) | MSH2, MSH6 | MSH2/MSH6 | AA |
| 9 | none identified | NA | NA | MSH2/MSH6 | AA |
| 10 | none identified | None identified | None identified | MSH2 | AA |
| 11 | none identified |
MSH2 rs587779143c, MSH2 c.A193T(K65X) |
None identified | MSH2/MSH6 | AA |
| 12 | none identified | MLH1 rs63750303c | MLH1 | MLH1/PMS2 | AA |
| 13 | none identified | MLH1 rs267607765c | MLH1 | MLH1/PMS2 | WEA |
| 14 | none identified | MSH2 c.1387+2A>T (2:47690168T>A) | None identified | MSH2/MSH6 | AA |
| 15 | none identified |
MSH2 rs28929484c MSH2 rs63750508c |
None identified | MSH6 | WEA |
| 16 | none identified | NA | NA | MSH2/MSH6 | WEA |
LLS, Lynch-like syndrome; LOH, loss of heterozygosity; LS, Lynch syndrome; MMR, mismatch repair; NA, tumor sample not available for study. AA: African American; WEA: West European American;
a
Patient was identified as a mutation carrier through the genetics clinic.
b
Loss of tumor MMR protein expression as assessed by immunohistochemistry.
c
Variant described as likely/pathogenic in ClinVar.
d
Variant described as uncertain significance in ClinVar