Lecture 37 - Cancer Genetics

Lecture 37 - Cancer Genetics - Describe the evidence of the...

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Describe the evidence of the genetic basis for cancer Explain the genetic mechanisms of cancer pathogenesis Describe genetic tools for the diagnosis of cancer Explain the application of cancer genetics in the therapy of cancer Vocab: oncogene, tumor suppressor gene, loss-of-heterozygosity, inherited cancer syndrome, Lynch syndrome Outline: 1. Introduction to cancer 2. Oncogenes examples of oncogene-mediated cancer 3. Tumor suppressor genes cancer disorders / syndromes involving them 4. DNA repair genes cancer disorders / syndromes involving them 5. Delineation of cancer syndrome Cancer Heritability: Insights from Twin Studies Twin cohorts from Sweden, Denmark, and Norway Heritability estimated via comparing degree of concordance for site-specific cancer phenotype between MZ and DZ twins Heritability estimates --- yes there is a genetic predisposition to cancer o Prostate CA (42%; 95%CI = 29-50%) o Colorectal CA (35%; 95%CI = 10-48%) o Breast CA (27%; 95%CI = 4-41%) What is cancer? Cancer cells have defects in regulatory circuits that govern normal cell proliferation and homeostasis Epigenetics – changes of the DNA/packing of the DNA Bad combo when oncogenes are turned on and the suppressor is turned off - Oncogenes 1911 – Peyton Rous discovered that a virus can cause sarcoma in chickens 1970 – Howard Temin and David Baltimore independently discovered that the genome of the Rous sarcoma virus is composed of RNA o a “reverse transcriptase” reverse transcribes the RNA into DNA upon infection in the cells of its host animal 1976 – Bishop & Varmus, retroviral oncogenes causative agents of cellular transformation, 1989 Nobel Prize 1979 – Robert Weinberg discovered that in many human tumors the same oncogenes of the retroviruses are mutated o Human versions of the viral genes - Oncogenes o Genes whose normal activity promotes cell proliferation o Gain of function mutations in tumor cells create forms that are inappropriately or excessively active. o A single mutant version of the gene may affect the cellular phenotype . o Non-mutant versions are called proto-oncogenes We all have this form in our body Most human cancer cells do not depend on viruses, but some do o Some needs viral to activate the cancer In cancer, the resident proto-oncogenes become activated via mutation or other means
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Describe the evidence of the genetic basis for cancer Explain the genetic mechanisms of cancer pathogenesis Describe genetic tools for the diagnosis of cancer Explain the application of cancer genetics in the therapy of cancer Vocab: oncogene, tumor suppressor gene, loss-of-heterozygosity, inherited cancer syndrome, Lynch syndrome Outline: 3. Introduction to cancer 4. Oncogenes examples of oncogene-mediated cancer 6. Tumor suppressor genes cancer disorders / syndromes involving them 7. DNA repair genes cancer disorders / syndromes involving them 8. Delineation of cancer syndrome Examples of Human Virus-Associated Cancers
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This note was uploaded on 09/14/2011 for the course PHARM HB taught by Professor Staff during the Spring '11 term at UCSD.

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Lecture 37 - Cancer Genetics - Describe the evidence of the...

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