9F292A72d01 - The Hallmarks of Cancer Chapter II Cancer...

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The Hallmarks of Cancer Chapter II Cancer Genetics Molecular Oncology 2009-2010
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Cancer Genetics according to Cancer Genetics according to Theodor Theodor Boveri Boveri Chromosomal theory of heredity (1902-1904) † 1915 Boveri showed that fertilization of sea-urchin eggs by two sperm eggs resulted in multiple cell poles. These cause unequal segregation of chromosomes: -specific chromosomes gave rise to particular fenotypes -genetic imbalance can result in death -individual chomosomes must carry different information
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Cancer Genetics according to Cancer Genetics according to Theodor Theodor Boveri Boveri Zur Frage der Enstehung Maligner Tumoren (1914) Boveri’s prediction •Cell-cycle checkpoints ( Hemmungseinrichting ) •The clonal origin of tumours •Genetic Mosaicism •Loss of cell adhesion in metastasis •Tumour-Suppressor genes ( Teilingshemmende Chromosomen ) •Cancer predisposition through inheritance of chromosomes that are less able to suppress malignancy •Inheritance of the same of ‘weak chromosome’ from both parents leads to homozygosity for the deffective chromosome and consequently, to high-penetrance cancer syndromes – for example xeroderma pigmentosum •The role of wounding and inflamation in tumour promotion •Sensitivity of malignant cells to radiation † 1915
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A comparison Normal and Cancer A comparison Normal and Cancer karyotypes karyotypes
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The balance of life The balance of life
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Cancer is a disease of our genes Cancer is a disease of our genes • The genetic instability driving tumorigenesis is fueled by: – DNA damage – Errors made by the DNA machinery MUTATIONS = DAMAGE - REPAIR
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Categories of Mutation involved in Categories of Mutation involved in human human tumours tumours (I) • Point mutation describes the substitution of one base pair of a DNA sequence by another. Intragenic bais pair substitution may have a number of effects depending upon its position: Substitution of one amino acid – MISSENSE mutation Base substitution result in a premature stop codon – NONSENSE mutation Base substitution near intron-exon junctions – abberant SPLICING effect Transversions (more frequent) Transitions
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Categories of Mutation involved in Categories of Mutation involved in human human tumours tumours (II) • Translocation • Hybrid chromosome result of the joining of part of one chromosome to another. Generates: – Structurally altered version of a gene and its protein – Gene under new transcriptional control • Gene Amplification • Several to thousand-fold gene amplification. Amplified genes may form two types of microscopically abnormal chromosomal configurations Double Minutes (DM) – Tiny paired extrchromosomal chromatin bodies that segregate randomly during mitosis.
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This note was uploaded on 05/28/2010 for the course WE MOBI000000 taught by Professor Geertberx during the Spring '10 term at Ghent University.

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9F292A72d01 - The Hallmarks of Cancer Chapter II Cancer...

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