Proto-oncogenes
From Ganfyd
A proto-oncogene is a normal gene whose function is to control cellular growth and differentiation that has the potential to become an oncogene by mutation or regulation changes. This key concept resulted in the nobel prize in 1989 for the discovery that transduction by retrovirus could result in the formation of an oncogene.
| Gene Name | Gene Locus | Malignancies associated with | Comments |
|---|---|---|---|
| BRAF (BRAF1, RAFB1) | 7q34 | Malignant melanoma, thyroid papillary cancer, thyroid anaplastic carcinoma, bowel cancer, adenocarcinioma of lung, non-Hogkins lymphoma | Codes for a serine/threonine kinase. Mutations also cause cardiofaciocutaneous syndrome |
| CBL(CBL2) | 11q23.3 | pre-B cell lymphoma, pro-B cell lymphoma, acute myeloid leukemia | Codes for a protein that is a negative regulator of several tyrosine kinase signaling pathways and is an adaptor protein in tyrosine phosphorylation-dependent signaling |
| EGF | 4q25 | malignant melanoma in mutation | Codes for epidermal growth factor. |
| EGFR (ERBB, ERBB1) | 7p12.3-p12.1 | Non small cell lung cancer, | Codes for epidermal growth factor receptor, a tyrosine protein kinase. Gefitinib works on mutated EGFR in nonsmall cell lung cancer. May be necessary for heart valve development |
| ERG (ERG1, ERG2) | 21q22.3 | Ewing sarcoma, prostate cancer | The early response gene codes for sequence-specific DNA-binding protein involved in differentiation of early hematopoietic cells. |
| ETS1 | 11q23.3 | Unclear but probably angiogensis promotor | Necessary in haematopoiesis. Transcription factor which activates transcription by interaction with purine-rich sequences present in the promoter/enhancer region of the TCRA gene. May promote angiogenesis. |
| FGFR1 (FLT2, FLG) | 8p11.2-p11.1 | FGFR1/BCR fusion gene in chronic myeloid leukemia, FGFR1/FGFR1OP2 in lymphoma, FGFR1/ZNF198 in lymphoblastic lymphoma | Codes for a fibroblast growth factor protein tyrosine kinase, whose mutations cause a large number of dysplastic sketal syndromes. |
| FOS (c-fos) | 14q24.3 | Osteosarcoma | The gene c-fos codes for a transcription factor (usually termed FOS) that forms dimers with Jun, acting at AP1 sites with a critical function in regulating development of skeleton. Mutations are associated with fibrous dysplasia. |
| FUS (TLS) | 16p11.2 | FUS/CHOP fusion gene in liposarcoma,FUS/ERG in acute myeloid leukemia, FUS/ATF1 in angiomatoid fibrous histiocytoma, FUS/CREB3L2 in fibromyxoid sarcoma | Codes a nuclear RNA-binding protein related to EWS that binds to RNA polymerase II |
| HRAS | 11p15.5 | Lung cancer, Bladder cancer, Rhabdomyosarcoma | Mutations cause Faciocutaneoskeletal syndrome(Costello syndrome) which has an increased risk of malignancy |
| JUNB | 19p13.2 | Hodgkin lymphoma, anaplastic large cell lymphoma | see putative oncogenes-JUN |
| KRAS2 (RASK2) | 12p12.1 | Bowel cancer, colorectal adenocarcinoma, Lung cancer, Breast cancer, Bladder cancer, Pancreatic cancer, Stomach cancer | A proto-oncogene. Mutations cause Noonan syndrome 3. |
| MAS1 | 6q24-q27 | epidermoid carcinoma | Codes an angiotensin mitogenic G protein-coupled cell surface receptor |
| MET(HGFR, RCCP2) | 7q31 | Papillary renal carcinoma, hepatocellular carcinoma | Codes for receptor-like tyrosine kinase |
| MLH1 | 3p21.3 | Bowel cancer | Codes for a DNA mismatch repair protein with mutations cause hereditary nonpolyposis colorectal cancer-2 (HNPCC2) |
| MLH3 | 14q24.3 | Bowel cancer | Codes for a DNA mismatch repair protein with mutations cause hereditary nonpolyposis colorectal cancer-7 (HNPCC7) |
| MSH2 | 2p22-p21 | Bowel cancer | Codes for part of the MSH2-MSH6 DNA mismatch repair (MMR) complex with mutations causing hereditary nonpolyposis colorectal cancer-1 (HMPCC1, FCC1, COCA1) |
| MSH6 (GTBP) | 2p16 | Bowel cancer, endometrial cancer | Codes for the ATPase part of the MSH2-MSH6 DNA mismatch repair (MMR) complex with mutations causing hereditary nonpolyposis colorectal cancer-5 (HMPCC5) |
| NRAS | 1p13.2 | Thyroid follicular carcinioma, Sarcoma, Rectal cancer | A proto-oncogene. |
| NTRK1 (TRK, TRKA) | 1q21-q22 | Papillary thyroid carcinoma | Codes for tropomyosin receptor kinase. Autoantibodies to this produce sensory axonal neuropathy and autonomic dysfunction. Singling pathway may be involved in acute myeloid leukemia. |
| PDGFB (SIS) | 22q12.3-q13.1 | Glioblastoma, dermatofibrosarcoma protuberans, meningioma | The gene for platelet-derived growth factor |
| PIM1 (PIM) | 6p21.2 | Prostate cancer, B cell leukaemia | Codes for a serine/threonine protein kinase |
| PIM2 | Xp11.23 | Prostate cancer | Codes for a serine/threonine protein kinase |
| PIM3 | 22q13 | Hepatoma | Codes for a serine/threonine protein kinase |
| PMS1 (PMSL1) | 2q31-q33 | Codes for mismatch repair protein whose mutations cause hereditary nonpolyposis colorectal cancer-3 (HNPCC3) | |
| PMS2 (PMSL2) | 7p22 | Bowel cancer, endometrial cancer, ovarian cancer | Codes for mismatch repair protein whose mutations cause hereditary nonpolyposis colorectal cancer-4 (HNPCC4) |
| SKI | 1p36.3 | Analogy with animal models in which over expression is permissive for malignancy | Codes for a protein in the TGFB1 signaling pathway |
| TGFBR2 | 3p22 | Bowel cancer | Codes for transforming growth factor beta receptor, a serine-threonine kinase. Mutations cause hereditary nonpolyposis colorectal cancer-6 (HNPCC6) |
| THRA (THRA1, ERBA, EAR7, ERBA1, THRA2, THRA3) | 17q11.2 | acute promyelocytic leukaemia | Codes for thyroid hormone receptor α |
| THRB (ERBA2, THR1) | 3p24.3 | Malignant lymphoma, salivary gland tumor,small cell cancer of lung | Codes for the thyroid hormone receptor β in the liver |
| TRK | 1q21-q22 | Papillary thyroid carcinoma | A chimeric gene formed through a somatic rearrangement involving the neighboring genes for neurotrophic tyrosine kinase receptor type 1 (NTRK1) and tropomyosin-3 (TPM3) |
| WNT1 (INT1) | 12q12-q13 | Widely expressed in cancer | Codes a secreted signling glycoprotein whose by either Wnt-1 small interference RNA or anti-Wnt-1 antibody induces apoptosis of cancer cells and inhibits tumor growth. |
