Examples of gene mutations implicated in CRC
| Gene or group of genes | Description | Mechanism for mutation increasing CRC risk | Notes |
|---|---|---|---|
| APC | Tumour suppressor gene | Inactivating mutation causes loss of regulation of spindle microtubules during mitosis7 | APC mutations cause chromosomal instability |
| TP53 | Tumour suppressor gene | Inactivating mutation causes loss of regulation of cell-cycle arrest and cell death3 | Inactivation may coincide with malignant transformation of adenomas3 |
| RAS | Oncogene | Activating mutations drive cell growth through MAPK pathway4 | KRAS mutation occurs as early event in adenoma-carcinoma sequence: concordance of primary tumour and metastases8 |
| BRAF | Oncogene | Activating mutations drive cell growth through MAPK pathway4 | |
| PIK3CA | Oncogene | Activating mutation upregulates PI3 K pathway, enhancing prostaglandin E2 synthesis and inhibiting apoptosis9 | Aspirin is a novel therapeutic agent for mutated PIK3CA tumours9 |
| MLH1, MSH2, MSH6, PMS2 | MMR genes | Inactivating mutation impairs ability to repair strand slippage within nucleotide repeats3 | MMR gene mutations cause microsatellite instability |
| EPCAM | Codes for transmembrane glycoprotein epithelial cell adhesion molecule | Deletion of 3′ end of EPCAM leads to epigenetic silencing of MSH210 | Novel cause of Lynch syndrome |
| MYH | Base excision repair gene | Germline inactivating mutation of MYH leads to somatic mutation of APC11 | Somatic mutations of MYH not described |
CRC, colorectal cancer; MAPK, mitogen-associated protein kinase; MMR, mismatch repair.