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Cancer Genetics - Coggle Diagram

- - - - Karyotype
      - aCGH
      - WGS
  - - - germline genotype, inherited genome which may include variants that increase risk for cancer
      - Increased lifetime risk if you had this kinda cancer-predisposing mutation
      - Present in ~10% of cancer patients
    - - variants in tumor cells only. Accumulaiton through selection over time, tumor gains more malignant features and usually takes years
- - - - TP53
        
        Li-Fraumeni
        
        Widespread veriety of tumor types
        
        Can be childhood onset
        
        almost fully penetrant
  - - - Important in tumor biology
- - - - overactive in tumors, has up-regulating activity
      - Only need one allele to be affected
      - Mechanisms of activation:
        
        Amplification
        
        Homogeneously staining regions (HSR)
        
        Gene is amplified in situ on original chromosome
        
        small copy number increases
        
        Too many gene copies = too much RNA/protien
        
        Double minute chromosomes (DM)
        
        thousands of copies of the gene floating around all alone
        
        point changes
        
        RAS genes/protiens
        
        Different types of RAS
        
        KRAS
        
        chromosome translocation
        
        Philadelphia chromosome
        
        a thing in the CML pathology
        
        Retroviral insertion
        
        Hypomethylation
        
        epigenetic alteration
        
        de-methylation can activate an oncogene
        
        aberrant splicing/isoforms
        
        RAS family of oncogenesis is commonly involved
      - If germline DNA has an activated oncogene then there is higher risk of the ≥1 cancer, earlier onset, and increased occurrence in other family members
        
        MEN2
        
        RET mutation
        
        Know MEN2A!
      - Oncogene addiction
        
        A tumor is dependent on an oncogene mutation to continue proliferating
        
        These could be good targets for therapy, but the tumor can lose that addiction wtih a subsequent mutation
      - Oncogenes activations are usually somatic, but can be germline
    - - Inheritance
        
        If it is inherited then there may be:
        
        Risk for multiple tumors
        
        earlier onset
        
        multiple family members affected
        
        Autosomal dominant cancer risk
        
        NF1
        
        Key concepts
        
        variable expressivity
        
        complex diagnostic criteria and complex management
        
        There are many NF1 mutations
        
        neurofibromas down-regulates RAS
        
        common autosomal dominant tumor syndrome
        
        "I'm sure you know more about this than I do. Why don't you tell me what's going on and what I can do for you?"
        
        That's heavy to make the decision not to have kids because it's too much to pass on.
        
        Recessive mechanism at cell level
        
        2 hit
        
        These are somatic and can be any type of mutation or hypermethylation
        
        When both of the tumor suppressor cells are inactivated
        
        Heterozygotes are fine... until the 2 hit
        
        Retinoblastoma
        
        Familial breast cancer
        
        sex influenced
        
        BRCA1 genotype
      - Some tumor suppressors cause different tumor types
      - Mutator genes
        
        These are a type of tumor suppressor
        
        these are mismatch DNA repair genes
        
        Lynch syndrome
        
        Instability in lengh of some microsatellites
        
        Microsatellite instability (MSI)
        
        Indicates a loss of a mutator gene in tumor DNA
        
        can be tested via IHC
        
        DNA shows novel alleles in the tumor that are not in germline genotype
        
        Mutation is due solely to mismatch repair genes (mutator genes)
      - Familial Adenomatous Polyposis (FAP)
        
        inherite APC gene mutation
        
        each polyp is the result of independent 2 hit which gain additional mutations and move toward malignancy
        
        thousands of polyps
        
        Subtype is Gardner Syndrome: tumors in other tissues as well