Table 3.
DNA Damage Repair Genes and CIN
| Human gene | Protein function | Gene alteration | Syndrome |
|---|---|---|---|
| BRCA1 | Sensor: BRCT containing | BRCA1: germline mutation BRCA2: germline mutation |
Hereditary breast-ovarian cancer |
| MRE11 | Sensor: DSB recognition/repair | Germline mutation Somatic mutation in MSI colon cancer |
Ataxia-telangiectasia–like disorder |
| BLM | Sensor: replication proteins | BLMAsh: increased risk of colon cancer | Bloom syndrome |
| WRN | Aberrant DNA methylation | Werner syndrome | |
| RTS | Rothmund–Thomson syndrome | ||
| ATM | Transducer: PI3-kinase (PIKK) | Germline mutation | Ataxia-telangiectasia |
| TP53 | Transducer: effector kinase | TP53: germline mutation | Li–Fraumeni syndrome |
| Somatic mutations | |||
| CHK2 | Transducer: effector kinase | Germline mutation | Li–Fraumeni–like syndrome |
| MYH | BER | MYH: germline mutation | MAP |
| MGMT | DNA damage repair | Aberrant DNA methylation | |
| BUB1 | Kinetochore regulation | Somatic mutation | |
| BUBR1 | Somatic mutation | ||
| MAD2 | Abnormal expression | ||
| hRod | Rare somatic mutation | ||
| hZw10 | Rare somatic mutation | ||
| hZwilch | Rare somatic mutation | ||
| CENP-A | Gene overexpression | ||
| CENP-H | Gene overexpression | ||
| HEC1 | Gene overexpression | ||
| AIM1 | Gene overexpression | ||
| INCENP | Gene overexpression | ||
| Ku70 | Nonhomologous end-joining | Loss of expression | |
| Ku86 | Loss of expression in rectal cancer | ||
| AURKA | Chromosome segregation defects | Gene amplification and overexpression | |
| TERC | Telomere regulation | Overexpression | |
| CCNE1 | Cell cycle regulation | Overexpression | |
| FBXW7/CDC4 | |||
| CDC25A ? | |||
| CDKN2A | Aberrant DNA methylation |
NOTE. Some genes that have been identified to cause cancer family syndromes or to be deregulated in human colon cancer. BRCT, Brca1 carboxy terminus; DSB, double-strand break.