molecular oncogenesis Flashcards
What are the gene targest-regulatory genes that lead to cancer?
protooncogenes -activation tumor suppressor genes -inactivation antiapotptosis genes -activation apoptosis genes -inactivation
protooncogene is what?
a normal regulatory gene; inolved in regulating normal cell growth; expression under tight control
What are oncogenes?
genes involved in autonomous unregulated cell proliferation in cancer cells
expression is constituitive
What are growth factors?
tumors acquire to ability to produce GF to which they are responsive
may develop GF receptors
cell proliferation results in further growth factor
What are the role of growht factor receptors as oncogenes?
normal transient activation; become oncogenes in overexpression or mutations ofr constituitive expression
What is the ERB B2 (Her2-neu) role in cancer?
amplification in breast cancer
poor prognostic sign
unresponsiveness to estrogen therapy
What is a the role of ras oncogene?
point mutation 15-20% of all tumors
GTP binding proteins with reduced GTPase activity
potential chemotherapy target
What is the role of c-ABL gene in oncogenesis?
transient tyroisine kinase activity
t(9,22) philadelphia chromosome creates a er-abl fusion
chronic myelogenous leikemia and acute lymphoblastic leukemia
constituitive activity
What are the role of transcription factor c-MYC in oncogenesis?
increased expression or mutation leads to different tumor
c-MYC overexpression translocation from 8-14 leads to Burkitt lymphoma
What is the role of n-MYC geen in oncogensis?
amplification in neroblastoma(25-30%)
poor prognosis
leads to constant signal for proliferation
What is the role of Rb protein in oncogenesis?
knock out of Rb lets cyclin D be constantly active instead of being witheld by Rb
What is the role of Cyclin D1 in oncogenesis?
mantle cell lymphoma
t(11,14)
cyclin D1-IgH fusion leads to overexpression
What is the retinoblastoma model?
mutation in both alleles for oncogenesis because it is a tumor suppressor gene
sporadic mutations lead to rare unilateral retinoblastoma
in familial retinoblastoma one abnormal gene more likely to occur in both eyes
“two-hit hypothesis”
What is the APC gene?
gene involved in destruction and thus down regulation of Beta-catenin
APC mutation is a two hi leading to Beta-catenin accumulation complements with TFC and grwoth
most involved in familial adenomatous polyposis
greater than 100 mucosal polyps
prophylactic colectomy
APC mutation
What is p53 function?
cell cycle arrest, intiation of apoptosis following DNA damage
What is Li-Fraumeni syndrome?
p53 mutation that leads to many different cancers at a young age
What is teh role of BCL2 inc ancer?
BCL2 is anti-apoptotic
overexpressed in many lymphomas
Especially follicullar lymphoma
t(14,18)–>overexpression
What are the carcinogenic categories?
microbes/viruses
chemicals
radiation
What are the two classifications of chemical carcinogenic compounds?
direct-acting carcinogens
-direct damage to dna
indirecct-actign carcinogens
- procarcinogen
- metabolism activates it
What is the effect of a polymorphism of CYPIA1?
10% caucasians have highly inducible form; leads to increased carcinogens; involved in polycyclic aromatics increase cancer
What is the effect of gutathione-S-transferase polymorphism?
50% of caucasians have deletion leading to increase cancer; lack of clearance
What is a initator carcinogen chemical?
direct and indirect; permanent damage to DNA targets vs repaired targets
What are promoter chemical carcinogens?
give a stimulus to cells to grow leading to increase cancer risk
What are the two types of radiation that lead to cancer genesis?
ionizing radiation -x-rays -gamma rays UV light -UVA -UVB -UVC
UV light leads to increase cancer so f what sort?
basal cell carcinoma, melanoma, and squamous cell carcinoma
formation of pyrmidine dimers
What are the mechanisms of oncogenesis of most infectious diseases?
viral genomic integration
stimulation of host inflammatory response with subsequent regeneration
What are hep B and hep C linked to as far as cancer?
chronic liver injury leading to regeneration; hepatocellular carcinoma
also HBx in hep B activates growth genes and inhibits p53
What is H. pylori linked to in onocgenesis?
gastric adenocarcinoma and extranodal marginal zone lymphoma;
hot inflammatory response leads to carcinogenesis of adenocarcinoma
or polyclonal expansion may select for population with aditional mutations lymphoma MALToma
What is BCR-ABL’s associated tumor?
CML ALL
What is bcl-2’s related tumor?
follicular and undifferentiated lymphoma
What tumor does BRAF cause?
melanoma
What tumor does ckit caues?
Gastroinitestinal stromal tumor
What tumor does cmyc cause?
Burkitt
What tumor does HEr2 mutations cause?
breast, ovarian and gastric carcionam
What tumor does Lmyc cause?
lung tumors
What tumor does N myc cause?
neuroblastoma
What tumor does ras cause?
colon cancer lung cancer pancreatic cancer
