Oncogenes

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Oncogenes, in its most general sense, are genes that are associated with malignancy, although strictly speaking, it usually refers to the result of mutated proto-oncogenes (see below).

Malignancy occurs when dysregulation of the such genes occurs, often through mutation. As there is extremely strong evidence that malignancy originates due to mutations of cellular DNA, these associations are important in understanding malignant transformation. However, such transformation is not simple and indeed oncogenes may be necessary or permissive and many genes also exist that prevent malignant transformation, the tumour suppressors. Mutations in these cause the formation of an oncogene. But other oncogenes are direct promoters of malignancy. Most of these also have roles as proliferation factors. A third class of cancer-related genes are stability or care-taker genes. These are responsible for maintaining the integrity and fidelity of DNA replication. A breakdown of these functions, does not in itself cause cancer, but instead permits accumulation of mutations which affect the proto-oncogenes and tumour suppressor genes.

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.

Many potential oncogenes also exist but may not have been proven to be definitely associated with malignant transformation in man. During preparation of these tables as might be expected some such in standard reference sources were found to have had fresh significant associations with human malignancy. All such lists need constant updating. That they have analogies with viral genomes or tumour inducing genes in other mammals however suggests that many will in due course be understood to have a role in oncogenesis.

The table below can't help but be incomplete. Over 600 genes may be upregulated in cancer, and it requires detailed experimentation to identify the 5 or 6 which have a key promoting or suppressing role.

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Some Human Oncogenes (Only ones definitely associated with human malignancy into this list please, others are found at putative oncogenes)
Gene Name Gene Locus Malignancies associated with Comments
ABL1 (ABL) 9q34.1 Chronic myeloid leukaemia see tyrosine kinase Abelson murine leukaemia protein
ABL2 (ABLL,ARG) 1q24-q25 acute myeloid leukaemia Member of the tyrosine kinase family. Important for synapse assembly and remodeling
AKAP13 (HT31, LBC. BRX) 15q24-q25 breast cancer Blast crisis oncogene
ARAF1 Xp11.4-p11.2 angioimmunoblastic lymphadenopathy with dysproteinemia Serine/threonine kinase
ARHGEF5 (TIM) 7q33-q35 Breast cancer Codes for protein that controls cytoskeletal organization through regulation of small GTP-binding proteins
ATF1 12q13 ATF1/EWS fusion gene associated with malignant melanoma of soft parts (MMSP) ATF1/FUS with histiocytoma. Codes for cAMP-dependent transcription factor-1
AXL 19q13.1-q13.2 Chronic myelogenous leukaemia transforming gene to acute leukaemia
BCL2 18q21.3 Burkitt lymphoma, follicular lymphoma Mediator of apoptosis. Translocation is marker of poorer therapeutic response
BRAF (BRAF1, RAFB1) 7q34 Hairy cell leukaemia, Malignant melanoma, thyroid papillary cancer, thyroid anaplastic carcinoma, bowel cancer, adenocarcinoma of lung, non-Hogkins lymphoma see proto-oncogenes
BRCA1 17q21 Hereditary breast-ovarian cancer syndrome. Familial Breast cancer, Papillary serous carcinoma of the peritoneum (PSCP), Prostate cancer see BRCA1.
BRCA2(FANCD1) 13q12.3 Familial Breast cancer, prostate cancer, pancreatic cancer see BRCA2
BRIP1 17q22.2 Ovarian cancer, breast cancer BRCA1 interacting protein C-terminal helicase 1 which is important in normal double-strand break repair
CBL (CBL2) 11q23.3 see proto-oncogenes
CSF1R (CSF-1, FMS, MCSF) 5q33.2-q33.3 Type M4 acute myeloblastic leukaemia and chronic myelomonocytic leukaemia Codes for for colony-stimulating factor-1 receptor, otherwise known as macrophage colony-stimulating factor
DAPK1 (DAPK) 9q34.1 Bladder cancer Codes for death-associated protein kinase a positive mediators of apoptosis induced by gamma-interferon.
DEK (D6S231E) 6p23 DEK/NUP214(DEK/CAN) fusion gene associated with acute myeloid leukaemia Codes for DNA binding protein involved in transcriptional regulation and signal transduction as a component of the splicing complex that remains associated with spliced exons.
DUSP6 (MKP3,PYST1) 12q22-q23 Non small cell lung cancer, pancreatic cancer Codes for member of mitogen-activated protein (MAP) kinase family and has key role in cellular signal transduction
EGF see proto-oncogenes
EGFR (ERBB, ERBB1) see proto-oncogenes
ERBB3 (HER3) 12q13 Non small cell lung cancer elevated ERBB3 mRNA levels in breast cancer
ERG see proto-oncogenes
ETS1 see proto-oncogenes
ETS2 Acute myeloid leukaemia Codes for a transcription factor
EWSR1 (EWS, ES, PNE,) 22q12 EWS/ERG in Ewing sarcoma, esthesioneuroblastoma EWS/FEV fusion gene in Ewing sarcoma, EWS/ZNF278 in small round cell sarcoma, EWS/FLI1 in Ewing sarcoma , EWS/ATF1 in malignant melanoma of soft parts(MMSP EWS/WT1 in desmoplastic small round cell tumor Ewing sarcoma breakpoint 1 gene
FES (FPS) 15q26.1 B cell lymphoma, acute promyelocytic leukaemia, bladder carcinoma, lung cancer, breast cancer, colon cancer, neuroblastoma, pre-B lymphocyte neoplasm, plasmacytoma, multiple myeloma, T cell lymphoma, sarcoma Codes for a tyrosine-specific protein kinase with a role in regulating immune response
FGF4 (HSTF1, KFGF) 11q13 Stomach cancer, kaposi sarcoma A fibroblast growth factor Important in limb development.
FGFR1 see proto-oncogenes
FGFR10P (FOP) 6q27 FGFR1/FGFR1OP2 fusion gene in non-Hodgkin lymphoma
FLCN 17p11.2 Renal cancer, bowel cancer see FFCN
FOS (c-fos) 14q24.3 see proto-oncogenes
FRAP1 see tumour suppressors
FUS (TLS) 16p11.2 see proto-oncogenes
HRAS 11p15.5 see proto-oncogenes.
GLI1 12q13.2-q13.3 Glioma, myxoid liposarcoma, salivary gland tumor Codes for a Kruppel (Kr) zinc finger protein
GLI2 2q14 Glioma Codes for a Kruppel (Kr) zinc finger protein
GPC3 Xq26 Germ cell cancer, Hepatocellular cancer see GPC3
HER2 (ERBB2, TKR1, NEU) 17q21.1 Breast cancer, lung cancer see HER2. Targeted by Trastuzumab.
HGF (SF) 7q21.1 Prostate cancer, renal cancer Codes for hepatocyte growth factor (hepatopoietin A, scatter factor) which is upregulated in many malignancies
IRF4 (LSIRF, MUM1) 6p25-p23 B-cell lymphoma, B-cell leukaemia, Multiple myeloma Codes for a interferon regulatory factor essental for lymphocyte function
JUNB 19p13.2 see proto-oncogenes
KIT(SCFR) 4q12 Gastrointestinal stromal tumour (GISTs), mast cell leukaemia, mastocytosis, seminoma and dysgerminoma Transmembrane tyrosine kinase receptor for stem cell factor (SCFR) is required for haematopoiesis, melanogenesis and gametogenesis. Mutations cause piebaldism.
KRAS2 (RASK2) 12p12.1 see proto-oncogenes.
LCK 1p35-p34.3 Non small cell lung cancer, Neuroblastoma, non-Hodgkin lymphoma codes for lymphocyte specific protein tyrosine kinase
LCO 2q14-q21 Hepatocellular carcinoma
MAP3K8(TPL2, COT, EST) 10p11.2 Ewings sarcoma, adenocarcinoma of lung, thyroid carcinoma Codes for a serine-threonine protein kinase.
MCF2 (DBL) Xq27 Breast cancer Codes for a GDP-GTP exchange factor that modulates the activity of small GTPases of the Rho family
MDM2 12q14.3-q15 Multiple MDM2 acts as a major regulator of the tumor suppressor p53 by targeting its destruction. Direct association of p53 with the protein MDM2 results in ubiquitination and subsequent degradation of p53
MET(HGFR, RCCP2) 7q31 see proto-oncogenes
MLH type genes see proto-oncogenes
MMD 17q Non small cell lung cancer, hepatocellular carcinoma, colon carcer Codes for monocyte to macrophage differentiation associated protein.
MOS (MSV) 8q11 Burkitt lymphoma, acute myeloblastic leukaemia Function in man unknown. Above associations indirect but analogous gene to Moloney murine sarcoma virus.
MRAS (RRAS3) 3q22.3 Activated in many tumors Codes for a RAS GTP-binding protein membrane-anchored, intracellular signal transducer
MSH type genes see proto-oncogenes
MYB (AMV) 6q22 Alterations found in more than a third of human solid tumour lines Encodes for proteins critical to hematopoietic cell proliferation and development
MYC 8q24.12-q24.13 Burkitt lymphoma Over expression in many malignancies, possibly associated with angiogenic, invasive promoting properties in excess. A transcription factor that promotes cell proliferation
MYCL1 (LMYC) 1p34.3 Small cell lung cancer, adenocarcinioma of lung, neuroblastoma
MYCN 2p24.1 Neuroblastomas Overlaps with NMYC and is transcribed from opposite DNA strand
NCOA4 (ELE1, ARA70, PTC3) 10q11.2 Prostate cancer Interacts with the androgen receptor in presence of dihydrotestosterone.
NF1 type genes see tumour suppressors
NMYC 2p24 Neuroblastomas, retinoblastoma Overlaps with MYCN and is transcribed from opposite DNA strand. Probably a DNA-binding protein.
NRAS 1p13.2 see proto-oncogenes.
NTRK1 (TRK, TRKA) 1q21-q22 see proto-oncogenes.
NUP214 (CAN, D9S46E) 9q34.1 NUP214/DEK fusion gene associated with acute myeloid leukaemia, NUP214/ABL1 associated with T-cell acute lymphoblastic leukaemia (T-ALL). Codes for nucleoporin component of the vertebrate nuclear pore complex.
OVC 9p24 Ovarian adenocarcinoma Abnormal in about 40% ovarian adenocarcinoma
TP53 (P53) 17p13.1 see tumour suppressors
PALB2 16p12 Breast cancer see PALB2
PAX3 (HUP2) STAT1 2q35 Alveolar rhabdomyosarcoma Transcriptions factor, causes some formms of Waardenburg syndrome and regulates RET.
PDGFB (SIS) see proto-oncogenes
PIM genes see proto-oncogenes
PML (MYL) 15q22 see tumour suppressors
PMS (PMSL) genes see tumour suppressors
PPM1D (WIP1) 17q22-q23 Breast cancer, Osteosarcoma Codes for a serine/threonine protein phosphatase that attenuates apoptosis and facilitates transformation of primary cells in cooperation with RAS
PTEN (MMAC1) 10q23.31 see tumour suppressors
PVT1 8q24 Burkitt lymphoma
RAF1 (CRAF) 3p25 Stomach cancer, renal cancer, glioblastoma, laryngeal cancer A regulator of endothelial cell survival during angiogenesis. Activated RAF counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2).
RB1 (RB) 13q14.1-q14.2 Retinoblastoma, osteogenic sarcoma, small cell carcinioma of lung, bladder cancer see RB1
RET 10q11.2 Multiple endocrine neoplasia type 2a and 2b and Medullary thyroid carcinoma see RET
RRAS2 (TC21) 11pter-p15.5 Teratocarcinoma, ovarian cancer Single point mutation activates its oncogene potential
ROS1 (ROS, MCF3) 6q22 Glioblastoma and probably others ROS1/FIG fusion protein is a tyrosine kinase found in astrocytoma
SMAD type genes see tumour suppressors
SMARCB1 (SNF5, INI1) 22q11 see tumour suppressors
SMURF1 7q21.1-q31.1 Pancreatic cancer Codes for a HECT domain E3 ubiquitin ligase that regulates tumor cell plasticity and motility through degradation of RhoA
SRC (AVS) 20q12-q13 hepatic metastatic bowel cancer, colon cancer, leukaemia Intracellular communication regulator protein. Mutations are activating, transforming, tumorigenic, and metastasis-promoting
STAT1 2q32.2-q32.3 Non small cell lung cancer see STAT1
STAT3 17q21 Epithelial cancers Codes signal protein that induces cell transformation through a combined inhibition of apoptosis and cell-cycle activation
STAT5 17q11.2 Permissive for a wide range of malignancies Codes signal protein that induces cell transformation through a combined inhibition of apoptosis and cell-cycle activation
TDGF1 (CRGF) 3p23-p21 teratocarcinoma Probably codes for signaling protein for mesoderm development
TGFBR2 3p22 see proto-oncogenes
THRA (ERBA, EAR7 etc) see proto-oncogenes
TFG (TRKT3) 3q11-q12 Papillary thyroid carcinoma Chimeric oncogene with NTRK1 proto-oncogene
TIF1 (TRIM24, TIF1A) 7q32-q34 Fusion genes associated with papillary thyroid carcinoma and myleoproliferative disorder. Codes for transcriptional intermediary factor 1
TNC (TN, HXB) 9q33 Neurofibromatosis type 1, Pancreatic cancer see TNC
TRK 1q21-q22 see proto-oncogenes
TUSC3 8p22 see tumour suppressors
USP6 (TRE2) 17p13 Multiple cancers Codes for a ubiquitin-specific protease found only in primates
WNT1 (INT1) 12q12-q13 see proto-oncogenes
WT1 11p13 Wilms tumour, over expressed in breast and lung cancer, myelodysplastic syndrome and acute myeloid leukaemia A zinc finger DNA-binding protein acting as a transcriptional activator or repressor depending on intracellular context
VHL 3p26-p25 see tumour suppressors

>>>Oncogenes/table

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