🧬 The “Cancer Gene Universe” in Numbers, if we chart all known cancer drivers:

1. 300 genes are implicated in cancer
2. 60 genes are major recurrent drivers
3. 15 genes cause the majority of cancers
4. TP53, KRAS, PIK3CA, APC, PTEN, BRAF are the global heavy hitters

Legend: TSG = Tumor suppressor gene, OG = Oncogene, DR = DNA repair

Gene             
% of Cancers 
Category 
Notes                                      
 
 
 
 
**TP53**         
**~50%**     
TSG      
Most common driver mutation in all cancers 
**KRAS**         
**25%**      
OG       
Dominant in pancreatic, lung, colon        
**PIK3CA**       
**14%**      
OG       
Breast, gynecologic, colon                 
**APC**          
**10%**      
TSG      
Initiator of colorectal cancer             
**PTEN**         
**9%**       
TSG      
Many solid tumors                          
**BRAF**         
**7%**       
OG       
Melanoma, thyroid                          
**RB1**          
**7%**       
TSG      
Retinoblastoma, lung                       
**NF1**          
**5%**       
TSG      
Nervous system tumors, others              
**ATM**          
**5%**       
DR       
DNA damage response                        
**IDH1/2**       
**4%**       
OG       
Glioma, leukemia                           
**CDKN2A**       
**4%**       
TSG      
Melanoma, pancreatic                       
**EGFR**         
**4%**       
OG       
Lung cancer                                
**SMAD4**        
**4%**       
TSG      
Pancreatic, colon                          
**ERBB2 (HER2)** 
**3%**       
OG       
Breast, gastric                            
**NOTCH1**       
**3%**       
OG/TSG   
Common in leukemias                        
**NFE2L2**       
**3%**       
OG       
Esophageal, lung                           
**CTNNB1**       
**3%**       
OG       
Liver, colon, endometrial                  
**ALK**              
~2%      
OG         
Lung, lymphoma                             
**ROS1**             
~1%      
OG         
Lung                                       
**MET**              
~1–2%    
OG         
Lung, kidney                               
**RET**              
~1–2%    
OG         
Thyroid, lung                              
**MYC**              
~1–2%    
OG         
Many aggressive cancers                    
**TERT promoter**    
~2–3%    
Regulation 
Important in brain, bladder, liver cancers 
**FAT1**             
~2%      
TSG        
Squamous cancers                           
**ARID1A**           
~2–3%    
TSG        
Ovarian, gastric                           
**BRCA1**            
~1%      
DR         
Breast, ovarian, prostate                  
**BRCA2**            
~2%      
DR         
Breast, prostate, pancreatic               
**MLH1**             
~1%      
DR         
Colon & endometrial                        
**PMS2, MSH2, MSH6** 
each ~1% 
DR         
MSI-high cancers                           
**FOXL2**         
<1%                        
Ovarian granulosa tumors        
**KIT**           
<1–2%                      
Melanoma & GIST                 
**GNAQ/GNA11**    
<1%                        
Uveal melanoma                  
**EWSR1 fusions** 
rare                       
Ewing sarcoma                   
**SS18 fusions**  
rare                       
Synovial sarcoma                
**NPM1**          
<1% overall (but ~30% AML) 
Leukemia                        
**FLT3**          
<1% overall (but 25% AML)  
Leukemia                        
**RUNX1**         
<1% overall                
Leukemia                        
**HOXB13**        
<1%                        
Prostate                        
**VHL**           
<1% overall                
Kidney cancer                   
**TERT promoter** 
varies                     
Brain, liver, thyroid, melanoma 

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#      
Cancer Type                           
Key Mutated Genes / Pathways                            
 
 
 
**1**  
**Glioblastoma (GBM)**                
TERT promoter, EGFR, PTEN, TP53, IDH-wildtype           
**2**  
Lower-Grade Glioma                    
IDH1, IDH2, 1p/19q codeletion, TP53, ATRX               
**3**  
Medulloblastoma                       
CTNNB1, PTCH1, SMO, MYC, MYCN                           
**4**  
Meningioma                            
NF2, TRAF7, KLF4, AKT1, SMO                             
**5**  
Ependymoma                            
ZFTA–RELA fusions, NF2                                  
**6**  
**Lung Adenocarcinoma**               
EGFR, KRAS, ALK, ROS1, BRAF, MET, RET, ERBB2            
**7**  
Lung Squamous Cell                    
TP53, CDKN2A, PTEN, NFE2L2, PIK3CA                      
**8**  
Small-Cell Lung Cancer                
TP53, RB1, MYC amplification                            
**9**  
**Breast (general)**                  
PIK3CA, BRCA1/2, TP53, HER2 (ERBB2), GATA3              
**10** 
Triple-Negative Breast                
BRCA1-like profile, TP53, RAD51, PTEN loss              
**11** 
HER2+ Breast                          
ERBB2 amplification, PIK3CA                             
**12** 
Colorectal Cancer                     
APC, KRAS, TP53, BRAF V600E, SMAD4, MLH1/MSH2/MSH6/PMS2 
**13** 
Gastric Cancer                        
CDH1, TP53, ARID1A, PIK3CA, ERBB2                       
**14** 
Esophageal Adenocarcinoma             
TP53, ERBB2, SMAD4, CDKN2A                              
**15** 
Esophageal Squamous                   
TP53, NOTCH1, PIK3CA, NFE2L2                            
**16** 
**Pancreatic Ductal Adenocarcinoma**  
KRAS (>90%), CDKN2A, TP53, SMAD4                        
**17** 
Ampullary Cancer                      
KRAS, TP53, APC                                         
**18** 
Liver (Hepatocellular)                
TERT promoter, TP53, CTNNB1, AXIN1                      
**19** 
Cholangiocarcinoma                    
IDH1/2, FGFR2 fusions, KRAS, BAP1                       
**20** 
Gallbladder Cancer                    
TP53, KRAS, ERBB2, ARID1A                               
**21** 
**Prostate Cancer**                   
TMPRSS2–ERG fusion, PTEN, BRCA2, SPOP                   
**22** 
Bladder Cancer                        
TERT promoter, FGFR3, TP53, RB1                         
**23** 
Kidney (Clear-Cell RCC)               
VHL, PBRM1, SETD2, BAP1                                 
**24** 
Kidney (Papillary RCC)                
MET, FH, NF2                                            
**25** 
Wilms Tumor                           
WT1, WTX, CTNNB1                                        
**26** 
Ovarian High-Grade Serous             
TP53, BRCA1/2, CCNE1                                    
**27** 
Ovarian Clear Cell                    
ARID1A, PIK3CA                                          
**28** 
Endometrial Cancer                    
PTEN, PIK3CA, KRAS, POLE, MLH1                          
**29** 
Cervical Cancer                       
HPV E6/E7 (inactivates TP53 and RB1)                    
**30** 
Vulvar Cancer                         
TP53 or HPV-related alterations                         
**31** 
Testicular Germ Cell Tumor            
KIT, KRAS, NRAS, isochromosome 12p                      
**32** 
Penile Cancer                         
TP53, HRAS, HPV E6/E7                                   
**33** 
**Melanoma (cutaneous)**              
BRAF V600E, NRAS, NF1                                   
**34** 
Melanoma (acral/mucosal)              
KIT, NF1, BRAF (less frequent)                          
**35** 
Uveal Melanoma                        
GNAQ, GNA11, BAP1                                       
**36** 
Basal Cell Carcinoma                  
PTCH1, SMO (Hedgehog pathway)                           
**37** 
Squamous Cell Carcinoma (skin)        
TP53, NOTCH1/2, CDKN2A                                  
**38** 
Merkel Cell Carcinoma                 
MCPyV integration OR TP53/RB1 mutations                 
**39** 
**Acute Myeloid Leukemia (AML)**      
FLT3, NPM1, IDH1/2, RUNX1, TP53                         
**40** 
Acute Lymphoblastic Leukemia (ALL)    
BCR-ABL1, ETV6-RUNX1, MLL rearrangements                
**41** 
Chronic Myeloid Leukemia (CML)**      
BCR-ABL (Philadelphia chromosome)                       
**42** 
Chronic Lymphocytic Leukemia (CLL)**  
TP53, ATM, NOTCH1, SF3B1                                
**43** 
Hodgkin Lymphoma                      
PD-L1/PD-L2 amplifications, JAK2                        
**44** 
Non-Hodgkin Lymphomas                 
BCL2, BCL6, MYC rearrangements                          
**45** 
Multiple Myeloma                      
IgH translocations, MYC, KRAS, NRAS                     
**46** 
**Osteosarcoma**                      
TP53, RB1, ATRX                                         
**47** 
Ewing Sarcoma                         
EWS–FLI1 fusion                                         
**48** 
Synovial Sarcoma                      
SS18–SSX fusion                                         
**49** 
Rhabdomyosarcoma                      
PAX3–FOXO1 fusion (alveolar)                            
**50** 
Gastrointestinal Stromal Tumor (GIST) 
KIT, PDGFRA                                             
**51** 
Neuroblastoma                         
ALK mutations, MYCN amplification                       
**52** 
Thyroid Papillary                     
BRAF V600E, RET/PTC, NTRK fusions                       
**53** 
Thyroid Follicular                    
RAS mutations, PAX8–PPARG                               
**54** 
Thyroid Medullary                     
RET mutations                                           
**55** 
Parathyroid Cancer                    
CDC73                                                   
**56** 
Adrenal Cortical Carcinoma            
TP53, CTNNB1, IGF2                                      
**57** 
Pheochromocytoma                      
RET, VHL, SDHB/D, NF1                                   
**58** 
Mesothelioma                          
BAP1, NF2, CDKN2A                                       
**59** 
Thymoma / Thymic Carcinoma            
GTF2I, KIT, TP53                                        
**60** 
Salivary Gland Cancers                
MYB–NFIB (adenoid cystic), ETV6–NTRK3                   
**61** 
Head & Neck Squamous Cancer           
TP53, CDKN2A, NOTCH1, HPV E6/E7 (subset)                

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