Table 1.
Examples of aberrations in DNA damage responses in human sporadic cancers
| Molecule | Activation or inactivation | Type of aberrations | Type(s) of cancer | Frequency | Phenotypes | Reference(s) |
|---|---|---|---|---|---|---|
| ATM | Activation | Increased autophosphorylation | Bladder, breast cancers | 30–68% | Cancer barrier function | (16,18) |
| Increased copy number | Prostate cancers | ˜2% | (51) | |||
| Inactivation | Mutation | Pancreatic, lung, colon, endometrial, prostate, skin, kidney, breast, central nervous system, ovarian cancers | 1–7% | (49,50) | ||
| Hematopoietic and lymphoid malignancies | ˜11% | (49) | ||||
| Loss of heterozygosity, loss | Pancreatic cancers | ˜5% | (50) | |||
| Decreased copy number | Prostate cancers | ˜5% | (51) | |||
| Decreased expression | Breast, head and neck cancers | 25–75% | (54,55) | |||
| MRE11 | Inactivation | Decreased expression | Breast cancers | 7–31% | (19,54,56) | |
| Colorectal, gastric, pancreatic cancers with microsatellite instability | 67–100% | (19) | ||||
| RAD50 | Activation | Increased expression | Colorectal cancers | ˜24% | (21) | |
| Inactivation | Decreased expression | Breast cancers | 3–28% | (19,54,56) | ||
| Colorectal, gastric cancers with microsatellite instability | 28–71% | (19) | ||||
| NBS1 | Activation | Increased expression | Esophageal, head and neck, non-small-cell lung cancers, hepatomas | 40–52% | Poor prognosis | (19,20) |
| Inactivation | Decreased expression | Breast cancers | 10–46% | (19,54,56) | ||
| Chk1 | Activation | Increased phosphorylation | Cervical cancers | ˜25% | (27) | |
| Increased expression | Lung, liver, breast, colorectal, ovarian, cervical cancers | 46–100% | Resistance to chemotherapy, poor prognosis | (22–27) | ||
| Inactivation | Decreased expression | Lung, ovarian cancers, hetapocellular carcinomas | 9–32% | (22,23,26) | ||
| Chk2 | Activation | Increased phosphorylation | Bladder, colon, lung cancers, melanomas | 30–50% | Cancer barrier function | (16,17) |
| Increased expression | Ovarian cancers | ˜37% | (26) | |||
| Inactivation | Decreased expression | Breast, non-small cell lung cancers | 28–47% | (57,58) | ||
| p53 | Inactivation | Mutation | Solid tumors | ˜50% | (47) | |
| Hematopoietic malignancies | ˜10% | (47) | ||||
| Decreased expression | Solid and hematopoietic tumors | ˜50% | Resistance to chemotherapy, poor prognosis | (48) | ||
| CDC25A | Activation | Increased expression | Thyroid, breast, ovarian, liver, colorectal, laryngeal, esophageal cancers, non-Hodgkin's lymphomas | 17–70% | (28) | |
| CDC25B | Activation | Increased expression | Thyroid, breast, ovarian, liver, gastric, colorectal, laryngeal, esophageal, endometrial, prostate cancers, gliomas, non-Hodgkin's lymphomas | 20–79% | (28) | |
| CDC25C | Activation | Increased expression | Colorectal, endometrial cancers, non-Hodgkin's lymphomas | 13–27% | (28) | |
| DNA-PKcs | Activation | Increased expression | Glioblastoma, prostate cancers | ˜49% | Poor survival | (29,30) |
| RAD51 | Activation | Increased expression | Breast, head and neck, non-small-cell lung cell, pancreatic cancers, soft tissue sarcomas | 24–66% | Resistance to platinum agents, poor outcome | (31–35) |
| Inactivation | Decreased expression | Breast, colorectal cancers | ˜30% | (59,60) | ||
| BRCA1 | Activation | Increased expression | Lung cancers | ˜22% | Resistance to chemotherapy | (36) |
| Inactivation | Mutation | Breast, ovarian cancers | <10% | (52,53) | ||
| Decreased expression | Breast, ovarian, lung cancers | 9–30% | (60–62) | |||
| BRCA2 | Inactivation | Mutation | Breast, ovarian cancers | <10% | (52,53) | |
| Decreased expression | Ovarian cancers | 13% | (61) | |||
| ERCC1 | Activation | Increased expression | Colorectal, ovarian, gastric, head and neck, non-small-cell lung cancers | 14–70% | Resistance to platinum agents | (31,37–43) |
| Inactivation | Decreased expression | Colorectal, gastric, non-small-cell lung cancers | 30–77% | (37,38,42,43) | ||
| APE1 | Activation | Increased expression | Bladder, breast, cervical, head and neck, liver, non-small-cell lung cancers, ovarian cancers, medulloblastomas, gliomas, osteosarcomas, germ cell tumors | 19–99% | Resistance to chemotherapy and/or radiation | (44) |
| PARP | Activation | Increased expression | Breast cancers, germ cell tumors | 5–47% | (45,46) | |
| FANCA | Inactivation | Decreased expression/loss of expression | Acute myelogenous leukemias | 4–40% | (64,65) | |
| Mutation | Acute myelogenous leukemias | ˜7.6% | (64) | |||
| FANCC | Inactivation | Mutation, loss of heterozygosity | Pancreatic cancers | ˜9% | (64) | |
| FANCF | Inactivation | Decreased expression/loss of expression | Breast, cervical, head and neck, non-small-cell lung, ovarian cancers, acute myelogenous leukemias, germ cell tumors | 6.7˜30% | (64,65) | |
| FANCG | Inactivation | Loss of expression | Acute myelogenous leukemias | 27% | (65) |
Expression has been confirmed at mRNA and/or protein levels. Studies using cultured cancer cells are excluded.