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four classes of genes are the principal targets of cancer-causing mutations
- Growth-promoting proto-oncogenes
- Growth-inhibiting tumor suppressor genes
- Genes that regulate programmed cell death (apoptosis)
- Genes that regulate programmed cell death (apoptosis)
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8 hallmarks of cancer
- Self-sufficiency in growth factors
- Insensitivity to growth inhibitory signals
- Altered cellular metabolism
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade and metastasize
- Ability to evade the host immune response
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Normal cellular counterpart whose product promote cell proliferation
proto-oncogenes
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genes that promote autonomous growth, mutated genes that cause excessive cell growth
oncogenes
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products of oncogenes without regulatory function
oncoproteins
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Mutations or over-expressions of the proto-oncogene are
associated with certain glial tumors such as astrocytoma.
PDGF-β
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Mutation in the proto-oncogenes ERBB 1 or amplification
ERBB 2 is associated with adenocarcinoma of the lung and breast carcinoma respectively.
EGF-receptor family
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Can act in concert to reprogram somatic cells into pluripotent
stem cells
MYC Oncogenes
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Overexpression of growth factor genes
PDGF & TGFa
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Altered growth factor receptors
RET
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Mimicry of signal transducing proteins
RAS
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Oncoproteins as transcription factors
MYC
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governor of the cell cycle
RB gene
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guardian of the genome
TP53
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regulates cell growth at G1/S
RB protein
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Mutation associated with retinoblastoma and osteosarcoma
RB gene
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Most common target for genetic alteration
TP53
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Stops neoplastic transformation by cell cycle arrest through quiescence and senescence and initiation of apoptosis
P53
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Mutations are associated with Li-Fraumeni Syndrome
TP53
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down regulates catenin
APC protein
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Loss of ___ causes continuous WNT signaling and β-catenin
enters nucleus → Cell proliferation
APC
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Associated with Familial adenomatous polyposis.
APC gene
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Even in the presence of ample oxygen, cancer cells demonstrate a distinctive form of cellular metabolism characterized by high levels of glucose uptake and increased conversion of glucose to lactose (fermentation) via the glycolytic pathway
Warburg effect
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Pro apoptotic proteins
BAX. and BAK
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Anti apoptotic proteins
BCL-2 families: BCL2, BCL-XL, MCL-1
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Tumor cells must reach the underlying basement membrane traversing the connective tissue in the vascular basement membrane and into the circulation
Metastasize
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Invasion of the extracellular matrix and Vascular dissemination
Metastatic Cascade
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is the most commonly mutated genes in cancer
Tp53
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Hereditary nonpolyposis colon cancer (HNPCC) syndrome
What Inherited defects in DNA repair genes?
Microsatellite instability
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Xeroderma pigmentosum
What Inherited defects in DNA repair genes?
Nucleotide excision repair
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Blood syndrome, Ataxia telangiectasia, Fanconi anemia
What Inherited defects in DNA repair genes?
Recombination repair
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BRCA1 and BRCA2 gene defects are associated with familial breast cancer
What Inherited defects in DNA repair genes?
Recombination repair
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