ONCOGENES AND ASSOCIATED TUMORS

 1.Growth factor

• PDGF- acts on  PDGF Receptor- Astrocytoma( associated tumor due to mutation)

             mechanism: PDGF binds to PDGF receptor on the astrocytes. Due to mutation, the astrocytes start producing PDGF which again binds to the receptor and the cell grows nd divides continuously. An autocrine loop is formed leading to the tumor formation

                                   

2.Growth factor receptors

• ERBB2[HER2/neu] - Epidermal growth factor receptor- Invasive breast cancers
• RET- neural growth factor receptor- MEN 2A, MEN 2B, Medullary carcinoma of thyroid
• KIT- Stem cell growth factor receptor- GI stromal tumor, testicular seminoma, mast cell diseases, AML

       mechanism: The effect of a single signal is amplified and the cell grows out of control.

                                     

 →HER2/neu overexpression is treated by Trastuzumab

 →When patient has  MEN 2A/2B and has RET mutation, then prophylactically thyroid is removed to avoid medullary carcinoma of thyroid.

3.Signal Transducers

• RAS gene family- GTP binding protein- carcinoma, melanoma, lymphoma                                                                                                                                                                                                           mechanism: Generally, RAS is associated with growth factor receptor in an inactive GDP bound state. when growth factor binds to the receptor, the GDP is replaced by GTP. this complex sends signals to the nucleus which allows cell growth. GTPase activating protein(GAP) will help in conversion of GTP into GDP and stops multiple signals from being passed. Mutated Ras inhibits GAP and multiple signals are sent to the nucleus leading to tumor formation.
•     ABL - Tyrosine kinase - t(9;22) BCR -   CML and some types of ALL.

                                    

4. Nuclear regulators( act on transcription factors)

• c-MYC - Burkitt lymphoma
• N-MYC - Neuroblastoma
• L-MYC - Lung carcinoma                                                                                                                     mechanism: In c-MYC mutation, t(8;14) involving IgH leads to increased production of MYC which will lead to tumor of B cell...Burkitt lymphoma

                                   

5. Cell Cycle Regulators

•  CCND1 - cyclin- Mantle cell lymphoma
• CDK4- cyclin-dependent kinase- Melanoma                                                                                           mechanism: cyclin D/ CDK4 complex phosphorylates the retinoblastoma protein, which promotes progression through the G1/ S checkpoint in cell cycle.     

Mantle zone in the lymph node