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38 Cards in this Set
- Front
- Back
What is a cancer?
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Group of diseases that share similar features:
1. Uncontrolled cell growth 2. Invasive ability into surrounding tissues Cancer does not differentiate and instead die. |
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Is cancer genetic?
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Yes, but this does NOT mean that it is hereditary. When we say it is genetic diseas we mean it is due to mutations that occur in our genes.
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Cause of cancer?
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Mutations that are typically occuring in a single cell
1. Spontaneous errors during DNA replication 2. Induced errors when we have enviornment agents (carcinogens) which induce damage to our DNA such as radiation. |
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What are the 2 main categories of cancer genes: mutations will lead to development of cancer.
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1. Oncogenes: gain of function
2. Tumor suppressor genes: loss of function |
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What is the multi-hit concept of cancer initiation?
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Cancer does not occur after a single genetic change. It is when we cross a certain threshold of mutations do we actually have cancer developing.
Deregulation of cell increases-->cell fails to differentialte-->multiples w/o restraint. Normal cell-->tumor/precancerous cell-->cancer |
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Oncogenes
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Generally cause sporadic cancer, not usually hereditary.
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Proto-oncogene
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Normal state with no mutations occuring, regulates normal cell growth.
1. growth factors 2. growth factor receptors 3. signal transduction pathways (protein kinases) 4. transcription factors |
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Mutations in Proto-oncogenes cause?
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Become active oncogenes which have the potential to contribute to cancer.
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What is the structure/function of proto-oncogene?
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And INCREASED normal expression of proto-oncogene which stimulates cell division and proliferation causes cancer
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Oncogenes act as dominant, heterozyous, or recessive?
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Dominant gene
It takes only one copy of an oncogene (a mutated proto-oncogene)is sufficient to cause phenotype-a heterozygote |
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RET proto-oncogene
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Transmembrane tyrosine kinase receptor.
Normally induces signal transduction when bount to ligand. |
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RET oncogene
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-Usually a point mutation
-activates receptor even in absence of ligand |
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Disease as a result of RET oncogene?
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Multiple endocrine neoplasia (MEN2)
Autosomal dominant inheritance of RET oncogene. |
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Medullary thyroid carcinoma
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95-100% risk of development if have MEN2
-Typically develops by childhood-early adulthood -Age 5-25 for MEN2A -Infancy in MEN2B |
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What are the recommendations for Medullary thyroid carcinoma?
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Prophylactic thyroidectomy (removal of thyroid overwise we expect thyroid cancer to develop)
-By age 1 for MEN2B -By age 5 for MEN2A |
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Other features of MEN2
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1. Pheochromocytomas, adrenal gland tumors that are typically benign
2. parathyroid adenoma/hyperplasia, can become cancerous 3. MEN2B: mucosal neuromas of the lips and tongue, enlarged lips, marfanoid body (long) |
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Sporadic chrom mutations occur in many cells, are they cancerous?
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Sporadic chrom mutations occur in many cells, but majority are benign
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What happens if a chromosomal rearrangement affects a proto-oncogene or tumor-suppressor gene?
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It can lead to cancer
These are typically sporadic cancers, not inherited. |
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If we do a blood test on someone are we going to see cancer?
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No, they are only present in the cancer cells and not inherited.
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The Philadelphia chromosome
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translocation involving chrom. 9 & 22
Moves the proto-oncogene ABL from its normal position on chrom 9 to a place next to the BCR gene on chrom. 22 This alters function of the ABL gene-->increase tyrosine kinase activity-->increasing signal transduction in cell-->increasing cell proliferation |
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What chromosome is present in majority of patients with CML (chronic myelogenous leukemia)
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The Philadelphia Chromosome.
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Tumor-suppressor genes
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Involved in the hereditary forms of all cancer, generally inherited.
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What are the normal function of tumor-suppressor genes?
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1. Control cell cycle growth & replication
2. DNA repair and maintaining genomic integrity |
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Mutation in the tumor-suppressor gene leads to?
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Loss of function which leads to cancer INDIRECTLY by allowing other mutations to accumulate.
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How is the tumor-suppressor gene inherited?
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Autosomal dominant so heterozygotes usually develop disease.
Acts recessive at the cellular level, cancer does not develop until loss of function of both alleles |
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What is Knudson's two-hit hypothesis? The two hit model of carcinogenesis?
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1. Sporadic cancer
2. Hereditary cancer |
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Sporadic cancer
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1. Individual starts with 2 normal copies of any given tumor-suppressor gene
2. 1st hit/loss of one normal allel in one copy 3. 2nd hit/loss of 2nd allel and inactivates 2nd copy 4. Cancer! |
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Hereditary cancer
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1. One inherited mutation (born with 1st hit in all cell bodies)
2. It only takes one acquired mutation or 2nd loss 3. Cancer! |
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The 2nd hit in hereditary cancer
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Is a random event
Can see delayed age of onset or reduced penetrance. |
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What are some inactivation methods of the second allele in Hereditary cancer?
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1. Point mutation or deletion (seen in inherited)
2. Chromosome rearrangement 3. Mitotic non-disjunction: loss of entire chrom 4. Mitotic recombination: loss of normal gene 5. gene amplification: over-expression of other proteins can inactivate tumor-suppressor gene. |
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SporadicF Retinoblastoma
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60% of retinoblastoma
Rare to have two aquired mutations occur in the same cell |
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Hereditary Retinoblastoma
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40% of retinoblastoma
High # of predisposed cells (1-2 million retinoblasts) |
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Features of hereditary cancers
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1. Increased risk
2. Earlier age of onset 3. Bilateral/multifocal presentation: inc. chance of 2nd hit occuring 4. Multiple family members with related cancers 5. Rare or unsual cancers |
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p53 Gene
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encodes a transcription factor that normally responds to DNA damage
halts the cell in G1 phase of the cell cycle allowing for DNA repair If damage severe, it induces programmed cell death |
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What happens if we have a mutation in the p53 gene?
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cells can escape DNA repair/death bc it won't stop the cell cycle to allow this to happen
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What is the most common mutated gene in human tumors?
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p53 gene
50% of all human solid tumors Inherited p53 are rare |
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Li-Fraumeni syndrome LFS
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-Inheritance of p53 mutations
-characterized by many tumors: breast, colon carcinomas, brain tumors, leukemias, soft-tissue sarcomas, osteosarcomas, leukemias, and adrenal corticoid tumors -Person can have multiple tumor types w/ early age of onset -risk 50% by age 40, 85-90% lifetime |
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Classic LFS is defined by the following criteria
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1. A proband with a sarcoma diagnosed before 45 AND
2. A first-degree relative with any cancer under 45 AND 3. A first-or second-degree relative with any cancer under 45 or a sarcoma at any age |