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40 Cards in this Set
- Front
- Back
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What is one of the challenges with treating a given mass of cells with the same chemotherapy?
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Tumor cell variant heterogeneity may lead to a differential response to chemotherapy.
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What are the four main categories of genes responsible for tumorigenesis?
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oncogenes, tumor suppressor genes, apoptosis genes, and DNA repair genes
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When do tumor cells acquire the genetic ability to metastasize?
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Early in their progresson
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Are oncogenes typically inherited?
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No, typically they are somatic events.
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What are some examples of oncogenes that lead to increased production of secreted growth factor?
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glioblastoma-PDGF; sarcomas TGF-α (note: oncogenes are dominant gain-of-function mutations)
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What are some examples of oncogenes that led to constitutively turned on growth factor receptors?
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RET; FLT3; ERBB1
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What are some examples of oncogenes that lead to excessive production of signal transducers?
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RAS; BCR-ABL
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What's an example of an oncogene that leads to excessive production of a transcription factor?
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MYC
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What's an example of an oncogene that leads to excessive production of an apoptosis inhibitor?
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BCL2
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What's an example of oncogenes that are involved with the cell cycle?
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Cyclin D, CDKs and CDK inhibitors
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What is the mechanism by which MYC is made constitutively active?
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8-14 translocation next to an IG gene (causes Burkitt's lymphoma)
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What is the mot common proto-oncogene abnormality?
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RAS
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What does constitutively active RAS cause?
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The activation of the MAPK pathway, transcription, and cell cycle progression
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What protein acts as a break for functional RAS?
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GAP genes (hydrolyze GTP)
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What does the dysregulation of cyclins and CDKs cause?
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progression through the cell cycle (gain-of-function?)
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What does the dysregulation of CCKIs cause?
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progression through the cell cycle (loss-of-function)
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What is the function of the G1/S checkpoint?
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It checks for DNA damage and prevents replication of mutated DNA using genes like RAD and ATM.
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What is the function of the G2/M checkpoint?
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It monitors completion of DNA replication and determines whether the cell can safely enter mitosis and separate sister chromatids.
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The phosphorylation of whage gene is crictical for progression past the G1/S checkpoint?
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Rb
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What is a difference in progession to a malignant phenotype between diseases caused by oncogenes and tumor suppressor genes?
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Tumor suppressor genes follow Knudsen's hypothesis in which a second "hit" is required to the good gene before disease develops (loss-of-function mutations still have enough expression from the good allele to overcome disease).
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What's the difference between a gatekeep gene and a caretaker gene?
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A gatekeeper gene directly regulates the growth of tumors by inhibiting their growth or promoting their death. Caretaker genes maintain genomic stability.
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What is a landscaper gene?
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A landscaper gene is a gene that normally maintains a healthy microenvironment but in the presence of a mutation they increase the probability of a neoplasia (not as severe as gatekeeper or caretaker).
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How does the Rb gene regulate cell cycle progession and how is it regulated?
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Rb in the hypophosporylated states binds a transcription factor EF2 which then promotes the methylatations and deacytation of proteins with that promoter. This inhibits cell cycle progression. Cyclins and CDKs hyperphosphorylate Rb, causing it to disoccate from EF2, allowing EF2 to work normally as a transcription factor and promote G1 to S progression.
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What 4 regulators of G1 to S progression are associated with tumorigenesis?
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p16/INK4a, cyclin D, CDK4 and Rb1
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What is the significance of the p53 gene?
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It is the most impotant gene in shutting down cell cycle progression in cells with mutated DNA by activating temporary cell cylce arrest (quiescence), inducing permanent cell cycle arrest (sensescene), and triggering apoptosis.
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What significance do miRNAs have in tumorigenesis?
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They can be used to inhibit oncogenes (if functioning poorly this can lead to tumorigenesis). Over expression can inhibit tumor suppressor genes. P53 affects a number of these.
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What is the condition where a patient inherits the p53 mutation?
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The have Li-Fraumeuni syndrome (many organs affected).
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What is the role of APC and β-catenin in tumorigenesis?
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β-catenin is a transcription factor that is normally bound to E-cadherins (it dissociates during the wounding process, however). When it is present cytosolically it induces cell proliferation. APC binds β-catenin inhibiting cell proliferation. Dysruption of the system can lead to tumorigenesis. (WNT also acts by this pathway by inducing the dissociation of the β-catenin/APC "destruction" complex.)
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What is the significance of the bcl-2 gene?
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It is an apoptosis inhibitor that works by sequestering cytochrome c. (Cytochrome c induces the formation of caspase which degrades the DNA of the cell.)
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What is the name of a gene that acts counter to the bcl-2 gene (promotes apoptosis)?
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bax gene
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Why is telomerase important with respect to tumorigenesis?
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Most somatic cells are telomerase negative (germ cells are telomerase positive). Tumor cells acquire a positive telomerase activity and become immortal.
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What is the significance of epigenetics in cancer?
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Hypermethylation of tumor suppresion genes and hypomethylation of oncogenes can lead to tumorigenesis.
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What is the significance of CpG islands in cancer?
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They are in the promoter region of tumor suppressor genes (among others) and can be hypermethylated in tumorigenesis.
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What's the CSC theory?
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Cancer cells are like stem cells and can possess the ability to drive angiogenesis, be immunoevasive, and chemoresistant and radioresistant.
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What are the four different aspects of molecular oncology testing?
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diagnostic, prognotic, predisposition, and therapeutic
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How does gene expression profiling help to undertand a disease like large B-cell lymphoma?
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A disease that looks histologically similar can actually be classified genetically as two different genetic signatures.
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How do gene expression signatures help with carcinomas?
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They can help identify carcinomas of unknown primary origin.
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Which drug helps with preventing the BCR-ABL gene complex from inducing tumorigenesis?
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Gleevec
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Where do miRNAs bind?
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the 3' UTR of a mRNA target resulting in degradation or inhibition of translation
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How large are miRNAs?
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about 22 RNA nucleotides
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