oncogene
TRANSCRIPT
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Balbeer Singh1248126
SZABIST, Karachi
Oncogenes
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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
Oncoprotein
Proto-oncogene “Mutation” Oncogene
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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
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Functions of Proto-Oncogene
• Help to regulate Cell growth and differentiation
• Involved in Signal Transduction
• Involved in execution of Mitogenic Signals
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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)
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Mechanisms of Oncogene Activation
1. Point Mutation
H-ras [codon 12]
Normal CGC GlyBladder cancer CTC Val
2. Gene Amplification
Double minutes
HSRs
Normal copy Multiple copies
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3. Gene Translocation
Ex. Burkitt’s Lymphoma
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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.
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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
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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
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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 carcinomaVal Ala Gln bladder
carcinoma
K-ras Cys Ala Gln lung carcinomaArg Ala Gln lung carcinomaVal Ala Gln colon
carcinoma
N-ras Gly Ala Lys neuroblastomaGly Ala Arg lung carcinoma
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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 neuroblastomaretinoblastoma
L-myc 10-20-fold small-cell lung cancer
c-abl ~5-fold chronic myoloid leukemia
c-myb 5-10-fold acute myeloid leukemiacolon carcinoma
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Examples of Oncogenes: More Monsters due to Translocation
Neoplasm Translocation Proto-oncogene
Burkitt lymphoma t(8;14) 80% of cases c-myc1
t(8;22) 15% of cases t(2;8) 5% of cases
Chronic myelogenous t(9;22) 90-95% of cases bcr-abl2
leukemia
Acute lymphocytic t(9;22) 10-15% of cases bcr-abl2
Leukemia
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It is easy to kill cancer, but the challenge is keeping the patients
alive at the same time