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135 Cards in this Set
- Front
- Back
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What are the four classes of cancer genes? |
Oncogenes
inactive suppressor genes Apoptosis genes and DNA repair genes |
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What are adaptor proteins called?
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these are signal transducers
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What do proto-oncogenes do?
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these regulate cell proliferation/differentiation
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With oncogenes, what kind of activation results in self-sufficient growth?
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a SINGLE ALLELE results in self sufficient growth
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With suppressors, what kind of loss do you need?
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you need to lose Both copies for suppressors
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With growth factors, how many alleles are affected, and how?
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these are oncogenes, and only needs 1 mutated copy.
these produce a product, for which the cell has a receptor. |
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What does the SIS oncogene produce? What cancer is it associated with?
(ON TEST) |
SIS overproduces PDGF-B
and leads to Glioblastoma |
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What does the HST oncogene produce? what cancer is it associated with?
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HST makes FGF, which leads to gastic and kaposi sarcoma
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What are growth factor receptors? (structure)
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these are transmembrane proteins with a TYROSINE KINASE DOMAIN
Oncogenic receptors will dimerize and activate without binding growth factor |
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How many mutated copies of a Growth Factor Receptor do you need?
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just one- as it is an oncogene
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What is ERB B-1? how many mutated copies?
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this is a growth factor receptor oncogene.
this only needs 1 mutated copy |
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What is ERB B-1's overexpressed product?
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EGFR (epidermal growth factor receptor)- stimulates tumor growth on its own
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What kinds of cancer are associated with ERB B-1 Mutations?
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Carcinomas of the lung, head, and neck
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How is ERB B-1 cancer treated? Important!!
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monoclonal antibodies against its product EGFR (for mutated product)
and tyrosine kinase inhibitors (for over expression) |
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What cancer is caused by Her-2 neu?
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this causes breast cancer, and poor prognosis
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What is Her-2 neu treated with?
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Herceptin (Trastuzamab)
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What is Her-2 neu? how many mutated copies?
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this is a growth factor receptor, and an oncogene- so needs just one mutated cancer
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What is bad about trastuzamab?
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it is cardiotoxic!
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What Kind of mutation occurs with Her-2 neu?
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Overexpression
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What cancer is associated with RAS?
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ras causes adenocarcinomas
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What kind of mutation causes RAS to turn to an oncogene? what offending agent?
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point mutations that are caused by CHEMICAL injury
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How many alleles need to be damaged for RAS to produce cancer?
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Just one allele, as it is an oncogene
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What is RAS?
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this is a signal transducing protein, AKA a GTP binding protein.
This activates the MAP kinase pathway in response to growth signals binding |
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What is the most common oncogene mutation?
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RAS mutation
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What turns off RAS?
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GAP's GTPase-activating proteins which includes NF-1
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What is NF-1?
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this is a tumor suppressor, a GTPase- active protein.
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What does a mutated RAS do?
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this cannot be turned off with a GAP- which leads to persistent signal transduction
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What are the two most common cancer locations of RAS?
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colon and pancreas
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What activates cABL?
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this is activated by a t(9:22) translocation
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What is cABL?
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this is a fusion of BCR and ABL, it is a nonreceptor tyrosine kinase
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What cancer is associated with cABL?
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chronic myelogenous leukemia (CML)- and some acute lymphoblastic leukemias
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What is the treatment for the cancer caused by cABL?
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a tyrosine kinase inhibitor, : Imatinib mesylate
this leads to a CURE! awesome! |
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What is JAK2?
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this is a nonreceptor tyrosine kinase, part of the JAK-STAT pathway
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What is MYC?
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this is a transcription factor- the self sufficiency in growth signals. DNA binding!
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What do transcription factors do?
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these control entry into and progression though the cell cycle.
Transcription |
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How many alleles of MYC need to be mutated to cause cancer?
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Just one, because it is an oncogene
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What is the genetic dysfunction i Burkitt lymphoma? how does it turn on?
MUST KNOW |
MYC is constitutively activated by a t(8:14) MUST KNOW
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What is the genetic dysfunction in neruoblastoma/ poor prognosis? how does it turn on?
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N-MYC (neruo MYC) production is amplified in neuroblastoma w/ poor prognosis
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How do you detect tumors with MYC dysregulation?
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you karyotype, FISH for translocation
Or you karyotype with fish for double minutes/homogenous staining regions (amplification of MYC) |
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How are CDK's activated?
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by phosphorylation
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What cyclin and CDK are active during G1 to progress past the G1/S check point?
ON TEST |
Cyclin D and CDK4.
Cyclin D phosphorylates CDK4 to move past this check point |
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What does cyclin E do?
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this complex regulates progression through S phase, and initiation of DNA replication
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What does the G1/S check point look for?
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this looks for DNA damage
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What does the G2/M check point look for?
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this monitors completion of repair
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What types of mutations can turn Cyclin D into an oncogene?
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Overexpresion
Translocation Amplification |
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With tumor suppressors, how many copies must be lost to cause cancer?
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Usually both alleles are lost
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What do gate keeper genes do? (two main facts)
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these regulate cell growth- the brakes to cell proliferation
tumor suppressors are involved in cell differentiation |
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What 3 tumors are associated with Loss of heterozygosity?
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retinoblastoma |
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What is a CpG island?
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this is a cytosine-phosphodiester-guanine island that is common in Promoter Regions of genes
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What is the function of a CpG island?
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this inactivates 2nd X
genomic imprinting and stabilized coding DNA When the CpG is hypermethylated, it has these positive effects listed above |
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What does the CIP/WAF family do? When is it active?
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this blocks the actions of several cyclin/CDK complexes.
This is active throughout the cell cycle |
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What two important p##'s are in the CIP/WAF family? and when are they active?
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p21- induced by p53
p27- responds to TGF-B |
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What is the MAIN p## in the INK4 family?
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p16/INK4
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what does p16/INK4 do? and when?
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is binds to cyclin D-CDK4 complex, inhibiting it. occurs at the G1/S check point
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What is p16/INK4 inhibitory to?
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inhibitory to RB
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What induces p21?
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p53
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what induces p27?
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TGF-B
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What cancers goes with inhibitor p16 mutation?
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Familial melanoma
and HPV-cervical cancer |
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What does RB do?
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this is a tumor suppressor, Brake on advancement of G1-S check point. Inhibits E2F
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how many copies of RB do we need to lose to get cancer?
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it is a tumor suppressor, so we need to lose two
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What is the phosphorylation state of RB when it is ACTIVE?
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HYPOphosphorylation is the active state for RB (when RB keeps the brakes on, it is active)
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What phosphorylates (and thus INACTIVATES RB)?
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Cyclin D and CDK4 want to turn on the cell cycle, so they add phosphates, and inactivate RB
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What does HPV's E7 protein do?
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this neutralizes RB
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What are the two main cancers that are involved in RB mutation?
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Retinoblastoma and Osteosarcoma
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What ways can RB function be lost by?
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RB mutation
RB deletion Gene silencing by hypermethylation Cyclin D/CDK 4 activation -p16INK4 inactivation |
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What is the gene deletion that cause retinoblastoma?
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deletion 13q = retinoblastoma
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What kind of mutation usually inactivates p53?
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single point mutation
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What is the gene for p53? on what chromosome?
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TP53 on chromosome 17
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What percent of cancers demonstrate a homozygous loss of p53?
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half of ALL cancers
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What are the main three cancers associated with loss of p53?
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Breast, lung, and colon cancer
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What can a mutation of 1 p53 gene lead to?
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this can act as an oncogene!! even though it is a tumor suppressor |
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What things trigger p53 pathway?
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Anoxia, oncogene expression, damage to DNA, stressors
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What does stress induced p53 result in? 3 outcomes
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Arrest cell cycle- p21 activation (CDK inhibitor @ G1/S junction)
permanent cell arrest- cause apoptosis- BAX gene active |
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What is the regulator protein of p53, and what does it do?
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MDM2 chops up p53 as soon as its made, to make sure it has a short half life of action (and thus fewer results) |
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What happens in a cell without p53?
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if it gets DNA damage, it will NOT get to arrest the cell cycle (with p21- CDK inhibitor)
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What is the role of ATM and ATR?
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these read DNA damage, and when DNA damage is detected- they posphorylate, and activate p53 (which then leads to cell cycle arrest)
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What is p73 involved with?
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the apoptosis of chemotherapy damaged cells
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p53 is an oncogene, as well as a tumor suppressor, and a repair gene
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need to know!
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How does mutated p53 relate to prognosis?
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mutated p53 correlates with poor prognosis
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What 3 things mutate p53?
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benzoapyrene in tobacco smoke
alflatoxin, UV light |
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what 3 things render p53 nonfunctional?
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HPV, hepatitis B, EBV
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What is Liframueni syndrome?
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this a heterozygous p53 mutation, that confers a 25x risk of cancer by age 50 |
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what is senescence?
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loss of a cells ability to complete mitosis due to irreversible arrest of the cell cycle
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What does APC do?
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APC suppresses the oncogene B-catenin by degrading it
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What does B-catenin do?
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this maintains cell to cell adhesion by binding E-cadherin (maintains cohesion/adhesivenes)
ALSO- part of WNT signaling pathway- which translocates and activates transcription. |
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What happens when APC is mutated?
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when APC is mutated, it cannot degrade B-catenin, so it activates WNT transcription and thus proliferation
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What cancers are associated with APC?
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FAP (familial adenomatous polyposis)
colon polyps, colon cancers, and hepatic cancer |
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What do cadherins regulate
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this regulates cell to cell adhesion
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What does TGF-B do?
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this stimuates CDKI's p21, and p15 (which inhibit kinases)
Tumor suppressor |
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What signalling pathway does TGF-B use?
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this uses signaling pathway SMAD
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What does NF-1 do?
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this is a suppressor gene, this a GAP that inactivates RAS.
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How many genes of NF-1 need to be lost to form cancer?
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2 need to be lost, to have a constantly active RAS
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What cancer does NF-1 lead to?
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this leads to neurofibrosarcoma
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What does the NF-2 gene cause?
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this causes schwannomas, meningiomas, and bilateral acoustic neuromas
Of the 8th CN |
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What kind is the product of the NF-2 gene?
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Merlin/ neurofibromin 2
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What does Merlin/neruofibromin 2 do?
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this is involved in cell-cell junctions and signaling functions
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What are 80% of all cancers in adults related to?
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VHL gene
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What do VHL genes do?
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these are suppressor genes.
VHL blocks production of VEGF (so when VHL is knocked out, get alot of blood vessels) |
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What cancers are associated with VHL?
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renal cell carinoma ( NOT ANGIOSARCOMA-those are common in the liver)
pheochromocytoma |
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What does PTEN do?
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this is a dephosphorylator in general.
typically the brake of the pro-survival/pro-growth pathway : PI3K/AKT (increased PIP3) |
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What ways can PTEN be downregulated?
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deletion |
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What class is PTEN in?
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tumor suppressor
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What cancer is associated with homozygous PTEN mutation?
TEST! |
endometrial carcinoma!!
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What chromosome is associated with WT-1?
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chromosome 11 p13
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What cancer is associated with WT-1?
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Wilm's tumor, a pediactric renal cancer (nephroblastoma- compare to VHL's renal adenosarcoma)
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What are the functions of WT-1?
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both suppressor and oncogene
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What does PTEN upregulate?
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upregulates BAD
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What is BCL2?
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this is an anti-apoptotic signal/ Anti autophagy gene
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What DNA change causes BCL-2 overexpression?
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t(14:18) translocation
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What are the genetics of B-cell follicular lymphoma?
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This is BCL-2 overexpression due to a t(14:18) transloaction |
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How does PTEN affect autophagy?
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this will facilitate autophagy
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What are the autophagy inhibitors?
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AKt, BCL-2, mTOR (which opposed PTEN) |
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What are the two mismatch repair genes?
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MLH-1, MSH-2 (if it has 3 letters, and its name begins with M, its a mismatch)
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What is the inherited malignancy associated with mismatch repair?
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Hereditary nonpolyposis colon cancer syndrome
- inherited one defective mismatch repair gene |
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what defect accumulates in the genome of HNPCC?
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this has microsatellite instability-
these are small runs of about 6 repeated nucleotides in a row- and if the runs dont match in the benign and malignant tissue, then you know! |
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What disease is associated with defective nucleotide excision repair?
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this cause Xeroderma pigmentosum
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what happens to DNA in xeroderma pigmentosum?
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this has UV light cross linking pyrimidines, which then prevents DNA replication
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What three genes are involved in Homologous Recombination repair?
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BRCA1, BRCA 2, ATM
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What are people with BRCA1, BRCA2, and ATM mutations hypersensitive to?
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DNA damaging agents like Ionizing Radiation
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What does BRCA-1 do normally?
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this has a protein product that regulates transcription, regulates Estrogen receptor activity.
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How do you lose the second allele in BRCA-1
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hypermethylation
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What do short telomeres do to p53?
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short telomeres activate p53, and make it arrest the cell cycle, via senescence or apotosis
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What do blood vessels in tumors look like?
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unstable, abnormal structure and function- disorganized, leaky
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What are the two proangiogenic factors?
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VEGF
bFGF |
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What 3 things control the transciption of VEGF?
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hypoxia-inducing factor HIF-1 (brake is VHL)
RAS-MAP MYC |
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What is a potentent VEGF anti-cancer drug?
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Bevacizumab
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What are the anti-angiogenesis factors?
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Thrombosopondin-1 (induced by p53) |
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What two things are lost in the dissocation of cells from the ECM?
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lose E-cadherins
and reduce Catenin's |
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What 3 things help cancer degrade its way through the ECM?
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type 4 collagenase MMP3
Cathepsin D Urokinase Plaminogen activator |
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when cancer cells want to migrate, what two things lose their polarity?
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Laminin receptors
Fibronectin recetors |
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What two factors help cancer cells migrate
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Fibrnectin attachment
and Autocrine motility factor- which is a chemotactic factor. |
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how do macrophages and leukocytes affect migration of malignant cells?
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these HELP cancer cells move along!
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What CD do tumor cells attached to when metastisizing?
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CD44- this is the attachment for endothelial cells
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Where does breast cancer prefer to metastasize to?
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Bone, liver, lung
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what is the dominant metabolic pathway of cancer cells?
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cancer cells shift to aerobic glycolysis
this allows it to be visualized by PET scan Called the WARBURG effect |
