Flashcards in Lecture 47 Deck (16)
What is the tumor progression pathway?
what is the evidence of monoclonality?
1. examination of X-inactivation pattern in cancers
2. chromosomal abnormalities of cancers
3. multiple myeloma produce a monoclonal immunoglobulin
give evidence that cancers start from a single cell
How do mutations take place?
1. environmental factors ( exogenous and endogenous)
2. germline inheritance
3. spontaneous mutations
what gene mutations could lead to cancer development?
2. DNA repair genes
3. apoptosis regulation genes
4. tumor suppressor genes
what does a mutation in proto-oncogenes lead cause?
1. increase in one or more normal functions
2. new function is created
only a single allele is needed to be mutated
What do mutations in tumor suppressor genes lead to?
result in a loss of function
both alleles must be impacted
what do mutations in apoptosis regulation genes lead to?
gain or loss of function of the gene
either increase or decrease apoptosis
What do mutations in DNA repair genes lead to?
impair the cell's ability to recognize and repair nonlethal genetic damage
describe the MAP kinase pathway?
major cellular proliferative pathway
1. growth factor presence outside the cell
2. binding of the growth factor to the receptor
3. receptor autophosphorylation
4. exchange of GTP to GDP on RAS
5. RAS binds to RAF and cascade begins
6. up or down regulation of cell survival and proliferation
mutations of what 5 components of the MAP kinase pathway result in oncogene formation?
1. growth factors
2. receptors binding GF
3. tyrosine kinases
4. proteins with GTPase activity that are signal transducers
5. transcription factors
How is a growth factor receptor mutation involved with breast cancer development?
ERBB2 gene is amplified in approximately 30% of breast carcinomas leading to overexpression of the HER2 receptor and that in turn will lead to a constitutively active tyrosine kinase.
what are the two ways oncogenes are activated by gene amplification?
1. double minutes- extrachromosomal fragments
2. homogeneously staining regions- amplified oncogenes attached to the chromosome
What is herceptin (trastuzumab)?
a monocolonal antibody against the HER2 receptor, thus blocking activity
this drug will lead to the regression of the cancer
How can double minutes and homogeneously staining regions detected?
karyotyping or by FISH
What is ERBB1 and what happens if it is mutated?
a gene that encodes for the epidermal growth factors
point mutations in ERBB1 results in a constitutive activation of the EGFR tyrosine kinase
this mutation can be seen in lung cancer