Comprehensive Cancer Gene Alteration
| Gene Name | Description | Function | Risk Factors | Tumor Types Involved | Drug Treatments | Additional Information |
|---|---|---|---|---|---|---|
| ALK (Anaplastic Lymphoma Kinase) | Encodes a receptor tyrosine kinase involved in cell growth. | ALK is a signaling molecule that regulates cell division and survival. Mutations lead to uncontrolled cell growth. | Smoking, age, family history, genetic mutations (especially in neuroblastoma). | Non-small cell lung cancer (NSCLC), Anaplastic large cell lymphoma (ALCL), Neuroblastoma | Crizotinib, Ceritinib, Alectinib, Brigatinib | Mutations in ALK cause constitutive activation of signaling pathways like the MAPK and PI3K-AKT pathways. ALK inhibitors are used to target these mutations. |
| APC (Adenomatous Polyposis Coli) | Tumor suppressor gene involved in the Wnt signaling pathway. | Regulates cell adhesion and controls the degradation of β-catenin, which is crucial for cell proliferation. | Family history, inherited mutations (e.g., Familial Adenomatous Polyposis (FAP)), diet. | Colorectal cancer, Gastric cancer, Liver cancer | No direct treatment; chemotherapy, targeted therapies (e.g., Bevacizumab) are often used for APC-associated cancers. | Mutations in APC lead to the activation of the Wnt signaling pathway and are a key step in the development of colorectal cancer. |
| BRAF (B-Raf Proto-Oncogene) | Encodes a serine/threonine kinase involved in the MAPK signaling pathway. | BRAF mutation leads to abnormal activation of the MAPK pathway, promoting cell proliferation. | Family history, exposure to UV radiation, and certain genetic syndromes. | Melanoma, Colorectal cancer, Thyroid cancer, Lung cancer | Vemurafenib, Dabrafenib, Encorafenib | BRAF V600E mutations are particularly targeted by specific inhibitors in melanoma and other cancers. |
| BRCA1 (Breast Cancer 1) | Tumor suppressor gene involved in DNA repair, particularly in repairing double-strand breaks. | Acts in the repair of DNA through homologous recombination. Loss of function leads to genomic instability. | Family history, inherited mutations (autosomal dominant inheritance). | Breast cancer, Ovarian cancer, Prostate cancer, Pancreatic cancer | PARP inhibitors (e.g., Olaparib, Rucaparib), Chemotherapy (e.g., Carboplatin) | Mutations in BRCA1 increase the risk of breast and ovarian cancers. PARP inhibitors exploit defective DNA repair in BRCA-mutant cancers. |
| CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A) | Encodes proteins that inhibit cyclin-dependent kinases, preventing cell cycle progression. | Regulates the cell cycle by inhibiting CDK4 and CDK6, preventing uncontrolled cell division. | Family history, certain genetic syndromes (e.g., Familial melanoma syndrome). | Melanoma, Pancreatic cancer, Non-small cell lung cancer | No direct drug treatment for CDKN2A mutations; strategies often include immune checkpoint inhibitors like Pembrolizumab and Nivolumab for melanoma. | CDKN2A mutations are associated with a variety of cancers, particularly in familial melanoma. |
| CTNNB1 (Catenin Beta 1) | Encodes β-catenin, a protein involved in cell adhesion and the Wnt signaling pathway. | β-catenin mediates Wnt signaling, regulating cell proliferation and differentiation. | Family history, genetic disorders, liver cirrhosis, and hepatitis. | Hepatocellular carcinoma, Colorectal cancer, Endometrial cancer | No direct drug treatment; Wnt pathway inhibitors and chemotherapy are under investigation. | Mutations in CTNNB1 lead to dysregulated Wnt signaling, often driving hepatocellular carcinoma and other cancers. |
| EGFR (Epidermal Growth Factor Receptor) | A cell surface receptor involved in the regulation of cell growth and differentiation. | EGFR activation promotes cell survival and proliferation. Mutations can lead to unregulated signaling. | Smoking, exposure to environmental carcinogens, age, ethnicity (higher in Asians). | Non-small cell lung cancer (NSCLC), Head and neck squamous cell carcinoma (HNSCC) | Gefitinib, Erlotinib, Osimertinib (for specific mutations like EGFR T790M) | EGFR mutations are common in lung cancer, and targeted therapies like tyrosine kinase inhibitors are highly effective. |
| IDH1/IDH2 (Isocitrate Dehydrogenase 1/2) | Mutations in IDH genes lead to the production of 2-hydroxyglutarate, which inhibits normal cell differentiation. | IDH mutations alter cellular metabolism and epigenetic regulation, promoting tumorigenesis. | No direct environmental risk factors; inherited mutations in certain cancers. | Gliomas, Leukemia, Cholangiocarcinoma | Enasidenib (for IDH2 mutations), Ivosidenib (for IDH1 mutations) | IDH mutations are targeted by specific inhibitors that block abnormal metabolite production, with promising results in certain cancers. |
| KRAS (Kirsten Rat Sarcoma Viral Oncogene) | Encodes a GTPase involved in regulating cell division, survival, and differentiation. | KRAS mutation leads to constant activation of downstream signaling pathways, contributing to tumorigenesis. | Smoking, alcohol, and certain genetic syndromes. | Pancreatic cancer, Colorectal cancer, Lung cancer | No direct targeted treatment; combinations with MEK inhibitors (e.g., Trametinib) or Immunotherapy (e.g., Checkpoint inhibitors) | KRAS mutations are challenging to target directly but are involved in many cancers, especially pancreatic and colorectal cancers. |
| MLH1 (MutL Homolog 1) | A mismatch repair gene involved in repairing DNA replication errors. | MLH1 forms a protein complex that fixes DNA replication errors. Loss of MLH1 causes microsatellite instability (MSI). | Family history, inherited mutations (e.g., Lynch syndrome). | Colorectal cancer, Endometrial cancer, Ovarian cancer, Gastric cancer | Immunotherapy (e.g., Pembrolizumab, Nivolumab) for MSI-high tumors. | Loss of function of MLH1 leads to defective DNA repair and increased mutational load, making tumors more responsive to immunotherapies. |
| MUTYH (MutY DNA Glycosylase) | DNA repair gene involved in the base excision repair (BER) pathway. | MUTYH repairs oxidative DNA damage and is involved in base excision repair. Loss leads to DNA mutations. | Inherited mutations (e.g., MUTYH-associated polyposis). | Colorectal cancer, Gastric cancer, Endometrial cancer | No direct drug treatment; chemotherapy is typically used in MUTYH-associated cancers. | MUTYH mutations cause defective DNA repair, increasing the risk of multiple cancers, particularly colorectal cancer. |
| NF1 (Neurofibromin 1) | Tumor suppressor gene that regulates the RAS signaling pathway. | NF1 encodes a protein that negatively regulates RAS, controlling cell growth and differentiation. | Family history, genetic disorders (e.g., Neurofibromatosis type 1). | Neurofibromas, Gliomas, Malignant peripheral nerve sheath tumors (MPNSTs) | No direct targeted treatment; chemotherapy and radiotherapy are used in associated cancers. | NF1 mutations cause loss of inhibition of RAS signaling, contributing to the development of benign and malignant nerve tumors. |
| PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) | Encodes a catalytic subunit of the PI3K enzyme involved in cell growth and survival. | PIK3CA mutations lead to activation of the PI3K-AKT pathway, promoting uncontrolled cell growth. | Family history, certain types of breast cancer, obesity, and environmental factors. | Breast cancer, Endometrial cancer, Colorectal cancer, Glioma | PI3K inhibitors (e.g., Alpelisib), AKT inhibitors (e.g., Ipatasertib), mTOR inhibitors (e.g., Everolimus) | PIK3CA mutations activate the PI3K-AKT pathway, making tumors sensitive to PI3K pathway inhibitors. |
| PTEN (Phosphatase and Tensin Homolog) | A tumor suppressor gene that regulates the PI3K-AKT signaling pathway. | PTEN dephosphorylates PIP3, antagonizing PI3K signaling and controlling cell growth. Loss of PTEN leads to uncontrolled growth. | Family history, genetic syndromes (e.g., Cowden syndrome), environmental exposures. | Endometrial cancer, Prostate cancer, Breast cancer, Brain tumors (glioblastoma), Thyroid cancer | No specific drugs targeting PTEN; PI3K inhibitors (e.g., Idelalisib) and AKT inhibitors (e.g., Ipatasertib) are being investigated. | PTEN mutations lead to activation of the PI3K-AKT pathway, making this a target for novel therapies. |
| RET (Rearranged during Transfection) | Encodes a receptor tyrosine kinase involved in cell signaling. | RET mutations cause constitutive activation of RET signaling, promoting cell proliferation. | Family history, inherited mutations (e.g., Multiple Endocrine Neoplasia type 2). | Thyroid cancer (especially medullary thyroid cancer), Lung cancer, Pheochromocytoma | Cabozantinib, Vandetanib, Sunitinib | RET inhibitors are used in medullary thyroid cancer and other RET-driven malignancies. |
| SMAD4 (SMAD Family Member 4) | Tumor suppressor gene that mediates the TGF-β signaling pathway. | SMAD4 mediates TGF-β signaling, which regulates cell growth, differentiation, and apoptosis. | Family history (e.g., Peutz-Jeghers syndrome), environmental factors. | Pancreatic cancer, Colorectal cancer, Gastric cancer | No direct drug treatment; chemotherapy and radiotherapy are typically used in related cancers. | SMAD4 mutations often result in disrupted TGF-β signaling, leading to unchecked cell growth and metastasis in pancreatic and colorectal cancers. |
| TP53 (Tumor Protein 53) | A tumor suppressor gene involved in regulating the cell cycle and apoptosis. | TP53 plays a critical role in preventing genomic instability by inducing apoptosis in damaged cells. | Family history, environmental exposures (e.g., radiation), certain inherited syndromes (e.g., Li-Fraumeni syndrome). | Breast cancer, Lung cancer, Colon cancer, Ovarian cancer, Sarcoma | No direct TP53-targeted drug therapies, though immune checkpoint inhibitors are being explored in cancers with TP53 mutations. | TP53 is the most commonly mutated gene in human cancers and is crucial in regulating cell cycle checkpoints and apoptosis. |
| VEGF (Vascular Endothelial Growth Factor) | Involved in the formation of blood vessels (angiogenesis). | VEGF promotes angiogenesis, which provides tumors with oxygen and nutrients. | Hypoxia, certain tumors, smoking, and exposure to carcinogens. | Colon cancer, Breast cancer, Renal cell carcinoma, Lung cancer | Bevacizumab (Avastin), Ramucirumab | VEGF inhibitors are used to target tumor angiogenesis, slowing tumor growth by cutting off its blood supply. |