APC/Apc
|
>80 |
Adenomatous Polyposis Coli |
• Inactivation of APC is the initiating event in the majority of colorectal cancers 100
|
|
|
• APC is a negative regulator of the Wnt pathway |
|
|
• Hyperactivation of the Wnt pathway initiates development of CRC by stabilising the β‐catenin transcription factor, increasing expression of transcription factors such as c‐Myc and c‐Fos, which regulate expression of cell cycle genes |
TP53/Trp53
|
∼65 |
Tumor protein p53 |
• Loss of TP53 is associated with disease progression 101
|
|
|
• TP53 regulates expression of genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism |
KRAS/Kras
|
∼45 |
Kirsten rat sarcoma viral oncogene homolog |
• Mutation of KRAS (>75% of mutations are at codon 12) and BRAF cause activation of the Ras‐MAPK pathway and mutations in these genes are mutually exclusive 2
|
|
|
• Activation of Ras‐Mapk pathway is associated with disease progression and poor prognosis 102
|
BRAF/Braf
|
∼8 |
v‐raf murine sarcoma viral oncogene homolog B |
• Activation of the Ras‐MAPK pathway leads to activation of transcription factors such as c‐Myc, and c‐Fos, which in turn regulate expression of cell cycle genes |
FBXW7/Fbxw7
|
∼20 |
F‐Box And WD Repeat Domain Containing 7 |
• E3 ubiquitin ligase that targets cyclin E and c‐Myc (cell cycle regulators) for ubiquitin‐mediated degradation 103
|
|
|
• Low expression of FBXW7 is associated with poor prognosis 104
|
TGFBR2/Tgfbr2
|
∼12 |
Transforming growth factor, beta receptor 2 |
• Alterations in TGFβ pathway e.g. mutation of TGFBR2, SMAD2, SMAD3 and SMAD4, are associated with disease progression 93, 105
|
SMAD2/Smad2
|
∼7 |
SMAD family member 2, 3, 4 |
• The SMAD family are intracellular signal transducers that are activated by TGFβ receptors and act as transcriptional modulators. |
SMAD3/Smad3
|
∼5 |
|
|
SMAD4/Smad4
|
∼12 |
|
|
PTEN/Pten
|
∼10 |
Phosphatase and tensin homolog |
• PTEN dephosphorylates phosphoinositide substrates and negatively regulates intracellular levels of phosphatidylinositol‐3,4,5‐trisphosphate (PIP3) |
|
|
• Negatively regulates AKT/PKB signaling pathway |
CDK8/Cdk8
|
∼12 |
Cyclin dependent kinase 8 |
• CDK8 regulates the cell cycle by acting as a co‐activator for transcription of nearly all RNA Polymerase II‐dependent genes |