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Genes involved in cancer
Oncogenes Activated from protooncogenes Usually
enhance cell proliferation Tumor suppressor
genes Inactivated by mutation or deletion Usually
arrest cell proliferation
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Detection of Oncogenes in Human Tumors
DNA transfections
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Activation of ras Oncogenes by Point Mutations
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9 10 11 12 13

• Ras mutations in tumors usually involve codons
  12, 13, 59 and 61.
• Mutated ras is found in 50 of colorectal cancers
  and 95 of pancreatic cancers.

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Activation de la Voie des MAP Kinases
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Functions and Mechanisms of Activation of
Proto-oncogenes Products

• Protein phosphorylation.
• Can activate kinase activity of the protein.
• Can generate docking sites to recruit target
  proteins.
• Signal transmission by GTPases.
• Signal transduction.
• Ras family proteins are prototypical members.
• Proteins localized in nucleus.
• Control of progress through cell cycle.
• Involvement in DNA replication.
• Proteins that regulate cell death (apoptosis).

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From the Growth Factor to the Cell Cycle
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GTP
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Identification of Oncogenes at Chromosomal
Breakpoints

• Creation of the Philadelphia chromosome.
• Found in gt95 of Chronic Monocytic Leukemia
  patients.

• Chromosomes 9 and 22 contain the genes c-abl and
  bcr at their breakpoint, respectively.
• Formation of bcr-abl chimeric gene
• Formation of bcr-abl chimeric RNA
• Formation of bcr-abl chimeric protein

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Figure 2 A comparison of karyotypes.
a Chronic myelogenous leukaemia, showing the
typical 922 translocation and an otherwise
normal karyotype. b Non-small-cell
carcinoma of the lung, showing abnormalities
of both number and structure. The arrows
indicate aberrant chromosomes.