The genes most commonly involved (through inactivation, loss or mutation) during the molecular pathways from normal colorectal mucosa to CRC
| Serrated pathways | Adenoma-carcinoma sequence* |
|---|---|
| BRAF† | APC |
| KRAS‡ | KRAS |
| hMLH-1§ | p53 |
| p16 | SMAD4 |
| MGMT |
*Familial CRC proceeds down a very similar pathway to the adenoma-carcinoma sequence; in familial adenomatous polyposis a germline mutation in the APC gene is present while in Lynch syndrome a germline mutation in one of the DNA mismatch repair enzymes is present. In both conditions, the second allele of the corresponding gene is then lost or inactivated through mutation.
†Mutations in BRAF are an early event in the SSL pathway.
‡Mutations in KRAS are an early event in the TSA pathway.
§hMLH-1 is inactivated in the SSL pathway via the CIMP mechanism.
APC, adenomatous polyposis coli; CIMP, CpG island methylator phenotype; CRC, colorectal cancer; SSL, sessile serrated lesion; TSA, traditional’ serrated adenoma.