Examples of oncogenes Ras-GTPase -activated in many cancers C-MYC -Transcription factor - overexpressed in colon cancer, amplified in lung, rearranged in ymphoma Ret- tyrosine kinase -multiple endocrine adenomatosis type 2A (MEN2A) MET Tyrosine kinase- hereditary papillary renal cancer CDK4-Cell cycle- familial melanoma BCR/ABL Tyrosine kinase -chronic myeloid leukemia t(9; 22 ·BCL2 Anti-apoptosis- follicular lymphoma t(1418)
Examples of Oncogenes • RAS - GTPase - activated in many cancers • c-MYC –Transcription factor - overexpressed in colon cancer, amplified in lung, rearranged in lymphoma • RET - Tyrosine kinase - multiple endocrine adenomatosis type 2A (MEN2A) • MET - Tyrosine kinase - hereditary papillary renal cancer • CDK4 – Cell cycle - familial melanoma • BCR/ABL - Tyrosine kinase - chronic myeloid leukemia t(9;22) • BCL2 – Anti-apoptosis- follicular lymphoma t(14;18)
Activation mechanisms of proto-oncogenes (proto-oncogene -->oncogene Proto-oncogene DNA 入 Translocation or transposition gene moved to new locus, Gene amplification Point mutation under new controls multiple copies of the gene within the gene N M New neocene promoter Normal growth- Normal growth- Hyperactive or stimulating stimulating degradation- protein in excess protein in excess resistant protein
Activation mechanisms of proto-oncogenes (proto-oncogene --> oncogene)
Activation via chromosomal translocation Diagrammatic representation of Bcr gene on chromo Abl gene on chromosome 9 9: 22 chromosomal translocation seen in chronic myeloid leukemia breakpoint (CML), the formation of BCR-ABL TRANSLOCATION oncogene and its detection by FIsh. TRANSCRIPTION AAA fused Bcr/AbI mRNA TRANSLATION rotein (Encoded activated tyrosine kinase) LSI BCR/ ABL Dual Color, Dual Fusion Probe Philadelphia LSI BCR (22q11.2) chromosome 22q normal abnormal Adapted from Molecular Biology of the ce/5t edition and http://www.slh.wisc.edu/clinicallcytogenetics/fish/
◼ Activation via chromosomal translocation ◼ Diagrammatic representation of 9:22 chromosomal translocation seen in chronic myeloid leukemia (CML), the formation of BCR-ABL oncogene and its detection by FISH. (Encoded activated tyrosine kinase) Adapted from Molecular Biology of the Cell 5th edition and http://www.slh.wisc.edu/clinical/cytogenetics/fish/