|
Gene symbol | Gene name | Effect of alteration | Major associations with specific tumor types | Implicated therapy |
|
Protooncogenes and oncogenes |
BCR-ABL | Breakpoint cluster region, Abelson murine leukemia viral oncogene homolog fusion protein | Compromises fidelity of DNA repair, deregulates proliferation, impairs apoptosis and differentiation | Chronic myelogenous leukemia | Imatinib, dasatinib, |
HRAS/KRAS | Harvey/Kristen rat sarcoma viral oncogene homolog | Constitutively activates MEK/ERK progrowth signaling | Non-small cell lung cancer | Salirasib |
BRAF | v-Raf murine sarcoma viral oncogene homolog B | Constitutively activates MEK/ERK progrowth signaling | Melanoma, V600E or V600K mutations | Vemurafenib, dabrafenib |
BCL2 | B-cell lymphoma/leukemia-2 | Impairs apoptosis | Leukemia, lymphoma, melanoma | Venetoclax |
|
Tumor suppressor genes |
BRCA1/2 | Breast cancer 1/2 | Impaired DNA repair | Breast and ovarian cancers | PARP inhibitor (via synthetic lethality) |
|
Epigenetic modifying genes |
IDH1/2 | Isocitrate dehydrogenase | DNA hypermethylation, disrupts differentiation | Acute myeloid leukemia (AML) | AG120, AG221, AG881 |
EZH2 | Enhancer of zeste 2 polycomb repressive complex 2 subunit | Inhibits apoptosis, silences by H3K27 trimethylation | Lymphoma | Tazemetostat |
DOT1L | DOT1-like histone H3K79 methyltransferase | Inhibits differentiation and apoptosis | Mixed-lineage leukemia | Pinometostat |
DNMT | DNA methyltransferase | Disrupts normal patterns of DNA methylation | Breast and colon cancers, glioma, AML | Azacytidine, decitabine |
HDAC | Histone deacetylases | Disrupts normal patterns of histone acetylation | Gastric, breast, colorectal cancers | Vorinostat, romidepsin |
|
Other targets |
ER | Estrogen receptor | Sustains proliferative growth signals | Breast and ovarian cancers | Tamoxifen |
CD20 | B-lymphocyte antigen, cluster of differentiation (CD) 20 | Supports B-cell activation and cell cycle progression | B-cell lymphomas | Rituximab |
ERBB2 (HER2/neu) | Human epidermal growth factor receptor 2 | Sustains proliferative growth signals | Breast, ovarian, uterine, and lung cancers | Trastuzumab |
PD1 | Programmed cell death protein 1 (CD279) | Prevents activation of T-cells | Potentially targets all solid tumors | Nivolumab |
CTLA4 | Cytotoxic T-lymphocyte associated protein 4 | Prevents activation of T-cells | Potentially targets all solid tumors | Ipilimumab |
AP-1 | Activating protein 1 | Regulates gene expression controlling differentiation, proliferation, and apoptosis | Colorectal cancer  case study | Irbesartan (angiotensin II receptor antagonist) |
PML-RAR | Promyelocytic leukemia, retinoic acid receptor alpha fusion gene | Inhibits granulocytic differentiation | Acute promyelocytic leukemia | Retinoic acid |
|
Biomarkers for clinical agents |
APAF1 | Apoptotic protease activating factor 1 | Prevents apoptosis | Melanoma | Doxorubicin |
MGMT | O6-methylguanine-DNA methyltransferase | Reverses DNA damage | Glioma | Alkylating agents |
|