Samenvatting Moleculaire Genetica

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Samenvatting - Moleculaire Genetica

  • 1 Intro

  • Cancer cells often exhibit structured chromosomes of various sorts, the loss of entire chromosomes, the presence of extra copies of others, and the fusion of the arm of one chromosome with part of another.
  • What is an euploid karyotypic state?
    Euploidy implies that each of the autosomes is present in normally structured pairs and that the X nd Y chromosomes are present in the numbers appropriate for the sex of the individual carrying them.
  • Anaeuploidy (deviation from the euploid karyotype) is seen in many cancer cells.
  • The acquisition of extra copies of one chromosome or the loss of another can create a genetic configuration that somehow benefits the cancer cell and its agenda of runaway proliferation.
  • How is a mutation passed on to the next generation?
    Via the germ line. The responsible mutation must strike a gene carried in the genome of sperm or egg or in the genome of one of the cell types that are immediate precursors of the sperm or egg within the gonads.
  • Most cancer mutations are somatic mutations: may affect the particular cells in which such mutation strike but will have no prospect of being transmitted to the offspring of an organism.
  • - Many of the mutations that accumulate in the genome represent the consequences of occasional oversights made by the repair apparatus. 
    - Others are results of catastrophic damage to the genome that exceeds the capacities of the repair apparatus.
  • Which two groups of genes are there within mammalian cells?
    - Housekeeping: encode proteins that are required universally to maintain viability of all cell types throughout the body or to carry out certain biological functions common to all cell types. 
    - Tissue-specific: encode proteins and thus phenotypes that are associated specifically with this cell type.
  • What are transcription factors (TFs)?
    Proteins that coordinate the expression. Many of these proteins bind to specific DNA sequences in the control region of each gene (sequence motif) and determine whether or not the gene will be transcribed.
  • What is pleiotropy?
    The ability of a single TF )or a single gene that specifies this TF) to elicit multiple changes within a cell or organism. 

    * In the case of cancer cells, a single malfunctioning, pleiotropically acting TF may simultaneously orchestrate the expression of a large cohort of responder genes that together proceed to create major components of the cancer cell phenotype.
  • The expression program is dependent on the action of multiple TFs acting in combination on large numbers of gene promoters.
  • Myc: acts as an anti-pausing protein whose actions permit thousands of cellular genes to be fully transcribed.
  • What are the possible post-translation modification of the N-terminal tails of histones?
    1. Methylation
    2. Acetylation
    3. Phosphorylation 
    4. Ubiquitylation
  • 2 Nature of cancer

  • What is the difference between benign and malignant tumors?
    - Benign: grow locally without invading adjacent tissues. 
    - Malignant: invade nearby tissues and spawn metastases.

    * Some local tumors can suppress organs and are then classified malignant. 
    * Some benign tumors can cause death because of hormone overproduction: Thyroid adenomas result in hyperthroidism which results in actromegaly (excessive growth tissues).
  • Where does the majority of human tumors arise from?
    Epithelial tissues. These are the carcinomas.

    * Epithelial cell layers of the GI tracts (mouth, oesophagus, stomach, small & large intestine), skin, mammary gland, pancreas, lung, ovary, uterus, prostate, gallbladder & urinary bladder.
  • What is the epithelia?
    Epithelia are sheets if cells that line the walls of cavities and channels, or in the case of skin, serve as the outside covering of the body.
  • What is the basement membrane (basal lamina)?
    It separates the epithelial cells from the underlying layer of supporting connective tissue cells (stroma).
  • Endoderm: epithelia of lungs, liver, gallbladder, pancreas, osophagus, stomach & intestine. 
    Ectoderm: skin
    Mesoderm: ovaries
  • Which forms of carcinomas are there?
    - Squamous cell carcinomas: tumors that arise from epithelial cells forming the protective layers (seal cavity or channel). 
    - Adenocarcinomas: specialized epithelia cells that secrete substances into the ducts or cavities that they line.
  • Which nonepithelial cancers are there?
    1. Sarcomas: derived from connective tissues (mesoderm). 
    - Mesenchymal cell types: fibroblasts, adipocytes, osteoblasts, myocytes. 

    2. Hematopoietic tissues: blood forming tissues incl. Cells of the immune system. 
    - Leukemia & lymphomas.

    3. Central & peripheral nervous system: neuroectodermal tumors.
    - Ectoderm 
    - gliomas, glioblastomas, neuroblastomas, schwannomas, medulloblastomas.
  • What is transdifferentiation?
    Switching in tissue lineage and the resulting acquisition of an entirely new set of differentiated characteristics. 

    * MET - EMT
  • What is the hyperplastic state?
    Growths with excessive numbers of cells. However, the cells can still assemble into tissues that appears normal.
  • What is metaplasia?
    In metaplasia one type of normal cell layer is displaced by the cells of another type that are not normally present in this site within a tissue. Often in epithelial transition zones. 
    * Barrett's esophagus: the normally present squamous epithelium is replaced by secretory epithelial cells of a type usually found within the stomach.
  • What is the dysplastic tissue?
    Cells within a dysplasia are usually abnormal cytologically; the appearance of individual cells is no longer normal. 

    Is seen as the transitional state between completely benign growths and those that are premalignant, 

    * Polyps, adenomatous polyps, papillomas
    * respect the boundary created by the basement membrane
  • How does tumor progression go?
    Normal --> hyperplastic --> dysplastic --> neoplastic --> metastatic
  • What are some arguments for the monoclonality of tumors?
    - Myelomas: derived from B-cell precursor. All the myeloma cells in a patient produce the identical antibody molecule, indicating their descent from a single, common ancestor. 

    - Have the same peculiar chromosomal abnormality ; the clear result of a rare genetic accident is seen in all the cancer cells within a tumor mass.
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