| Gene (s) |
Mutation (s) |
Mechanism |
Phenotype |
| Mismatch Repair (MLH1, MSH6, PMS2, MSH2) |
Germline deletions, point, truncation, missense, or frame shift |
Abnormal MMR protein expression leading to faulty repair of DNA replication errors |
Early-onset colorectal cancer; increased risk of endometrial, ovarian, gastric, urinary tract, renal, biliary tract, brain, and small bowel cancers |
| Epithelial Cellular Adhesion Molecule (EPCAM) |
Germline deletion involving 3΄ exon |
Epigenetic silencing of neighboring MSH2 |
Early-onset colorectal cancer; increased risk of endometrial, bladder, small bowel, and appendiceal cancers |
| MLH1 |
Germline promoter hypermethylation |
Loss of MLH1 expression |
Tumor spectrum, phenotype, and incidence are under investigation |
| Cell Cycle Check Point Kinase 2 (CHEK2) |
1100delC and I157T |
Inactivation of CHEK2: a serine/threonine kinase with mutliple regulatory functions (cell cycle progression, apoptosis, DNA damage repair) |
1100delC: increased risk of breast, colon, and ovarian cancers; and various other Lynch-related malignancies
I157T: increased risk of breast, colon, kidney, prostate, and thyroid cancers |
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