Oncogene

Oncogene:, Definition, History, Activation and Mutations

1. Balbeer Singh 1248126 SZABIST, Karachi Oncogenes

2. Introduction Onco means Cancer Oncogene is a gene which in certain circumstances can transform a cell into a tumor cell. A  Proto-oncogene  is a normal gene that can become an oncogene due to mutations or Increased   expression The resultant protein encoded by an oncogene is termed O ncoprotein Proto-oncogene  “Mutation”  Oncogene

3. History The term “Oncogene " was coined in 1969 by  George Todaro and Robert Heubner . Of National Cancer Institute. The first confirmed Oncogene was discovered in 1970 and was termed  src In 1976 Drs. Dominique Stehelin ,  J. Michael  and  Harold E. Varmus  of the  University of California demonstrated that oncogenes were activated Proto-Oncogenes , found in many organisms including humans

4. Functions of Proto-Oncogene Help to regulate Cell growth and   differentiation Involved in  Signal Transduction Involved in execution of  Mitogenic Signals

5. Activation The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation : A  mutation  within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure. An increase in the amount of a certain protein A  chromosomal Translocation(another type of  Chromosome abnormality)

6. Mechanisms of Oncogene Activation 1. Point Mutation H- ras [codon 12] Normal CGC  Gly Bladder cancer CTC  Val 2. Gene Amplification Double minutes HSRs Normal copy Multiple copies

7. 3. Gene Translocation Ex. Burkitt’s Lymphoma

8. On chromosome 18, there's an oncogene  called  BCL2 In people with a certain kind of leukemia, this gene has been moved in its entirety from chromosome 18 to chromosome 14.

9. Result of Oncogenes Activation Overproduction of growth factors Flooding of the cell with replication signals Uncontrolled stimulation in the intermediary pathways Cell growth by elevated levels of transcription factors Cancer

10. Classification of Oncogene Secreted Growth Factors c-sis , hst Cell Surface Receptors erb B, fms , ret, trk , fes , fms Intracellular Transducers c- src , c- abl , mst , ras DNA-binding Nuclear Proteins myc , jun , fos Regulators of the Cell Cycle bcl , bax , bad

11. Examples of Oncogenes: More Monsters due to Point Mutations amino acid position Ras gene 12 59 61 Tumor c- ras (H, K, N) Gly Ala Gln normal cells H- ras Gly Ala Leu lung carcinoma Val Ala Gln bladder carcinoma K- ras Cys Ala Gln lung carcinoma Arg Ala Gln lung carcinoma Val Ala Gln colon carcinoma N- ras Gly Ala Lys neuroblastoma Gly Ala Arg lung carcinoma

12. Examples of Oncogenes: More Monsters due to Gene Amplification Oncogene Amplification Source of tumor c- myc ~ 20-fold leukemia and lung carcinoma N- myc 5-1,000-fold neuroblastoma retinoblastoma L- myc 10-20-fold small-cell lung cancer c- abl ~ 5-fold chronic myoloid leukemia c- myb 5-10-fold acute myeloid leukemia colon carcinoma

13. Examples of Oncogenes: More Monsters due to Translocation Neoplasm Translocation Proto-oncogene Burkitt lymphoma t(8;14) 80 % of cases c-myc 1 t(8;22) 15 % of cases t(2;8) 5 % of cases Chronic myelogenous t(9;22) 90-95% of cases bcr-abl 2 leukemia Acute lymphocytic t(9;22) 10-15% of cases bcr-abl 2 Leukemia

14. It is easy to kill cancer, but the challenge is keeping the patients alive at the same time